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Search Results (2,014)

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12 pages, 362 KiB  
Article
The Predictive Value of Red Cell Distribution Width in End-Stage Colorectal Cancers’ 6-Month Palliative Chemotherapy Response—A Single Center’s Experience
by Maciej Jankowski, Krystyna Bratos, Joanna Wawer and Tomasz Urbanowicz
J. Pers. Med. 2025, 15(8), 359; https://doi.org/10.3390/jpm15080359 (registering DOI) - 7 Aug 2025
Abstract
Backgrounds: The incidence of gastrointestinal cancers (GICs), though decreased in recent years, still accounts for 35% of all cancer-related mortality. The proper identification of risk factors, early diagnosis, and therapy optimization represent the three cornerstones of GIC treatment. In four-stage diseases, chemotherapy embodies [...] Read more.
Backgrounds: The incidence of gastrointestinal cancers (GICs), though decreased in recent years, still accounts for 35% of all cancer-related mortality. The proper identification of risk factors, early diagnosis, and therapy optimization represent the three cornerstones of GIC treatment. In four-stage diseases, chemotherapy embodies target therapy that may prolong patients’ expectancy when suitably applied. Patients and Methods: There were 133 (82 (62%) male and 51 (38%) female) consecutive patients with a median age of 70 (64–74) years who underwent palliative treatment due to four-stage colorectal cancer (CRC) between 2022 and 2024. The demographic, clinical, and laboratory data and applied chemotherapeutic protocols were evaluated regarding the response to applied therapy, resulting in complete or partial tumor regression. The advancement of the tumor was based on computed tomography (CT) performed before and 6 months after the chemotherapy. Results: The multivariable model revealed red cell distribution width (RDW) from peripheral blood analysis (OR: 0.81, 95% CI: 0.65–1.00, p = 0.049) as a possible predictor for systemic treatment response in colorectal cancer. The receiver operating characteristic curve revealed a predictive value of male sex and RDW prior to systemic therapy, with an area under the curve of 0.672, yielding a sensitivity of 70.0% and specificity of 58.1%. Conclusions: The results of our analysis point out the possible modulatory impact of RDW on six-month systemic therapy in colorectal terminal cancer management. Further studies are required to confirm the presented results. Full article
(This article belongs to the Special Issue Precision Medicine for Digestive Diseases)
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18 pages, 1528 KiB  
Review
Sex Differences in Colorectal Cancer: Epidemiology, Risk Factors, and Clinical Outcomes
by Sophia Tsokkou, Ioannis Konstantinidis, Menelaos Papakonstantinou, Paraskevi Chatzikomnitsa, Eftychia Liampou, Evdokia Toutziari, Dimitrios Giakoustidis, Petros Bangeas, Vasileios Papadopoulos and Alexandros Giakoustidis
J. Clin. Med. 2025, 14(15), 5539; https://doi.org/10.3390/jcm14155539 - 6 Aug 2025
Abstract
Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a [...] Read more.
Colorectal cancer (CRC) constitutes a major global health concern, ranking as the third most common cancer and the second leading cause of cancer-related mortality. The current review explores sex-based differences in CRC epidemiology, risk factors, tumor biology, and clinical outcomes. Males exhibit a higher incidence and mortality rate, with left-sided (distal) CRC predominating, while females are more frequently diagnosed with right-sided (proximal) tumors, which tend to be more aggressive and less responsive to conventional chemotherapy. Genetic disparities, including microsatellite instability and X-chromosome tumor suppressor genes, contribute to sex-specific differences in tumor progression and treatment response. Immune variations also influence disease outcomes, with females exhibiting stronger immune surveillance but higher exhaustion markers. Lifestyle factors such as body mass index (BMI), smoking, and hormonal influences further modulate CRC risk. While males are more vulnerable to obesity-related CRC, central obesity (waist-to-hip ratio) emerges as a stronger predictor in females. Additionally, smoking increases CRC risk differentially by tumor location. These findings underscore the importance of sex-specific approaches in CRC prevention, screening, and treatment, advocating for personalized medicine strategies tailored to gender-based biological and clinical distinctions. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: Outcomes and Therapeutic Management)
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7 pages, 1809 KiB  
Case Report
Seronegative Paraneoplastic Opsoclonus–Myoclonus–Ataxia Syndrome Secondary to Low Volume Endocrine-Sensitive Malignancy of Likely Breast Origin
by Geraint Berger, Caitlin Jackson-Tarlton, Daniel Rayson, Alexander Silver, Mark Walsh and Ashley Drohan
Curr. Oncol. 2025, 32(8), 440; https://doi.org/10.3390/curroncol32080440 - 6 Aug 2025
Abstract
A 51-year-old female presented to the emergency department with vertigo, visual disturbances, involuntary rapid repetitive eye movements, incoordination, and imbalance. Physical examination revealed opsoclonus, myoclonus, and bilateral limb and gait ataxia. Initial workup was negative for intracranial abnormalities, and no abnormalities were noted [...] Read more.
A 51-year-old female presented to the emergency department with vertigo, visual disturbances, involuntary rapid repetitive eye movements, incoordination, and imbalance. Physical examination revealed opsoclonus, myoclonus, and bilateral limb and gait ataxia. Initial workup was negative for intracranial abnormalities, and no abnormalities were noted on blood work or cerebrospinal fluid analysis. Tumor markers were within normal limits. As part of her diagnostic workup, a positron emission tomography (PET) scan was performed, which showed a highly FDG-avid solitary 7 mm left axillary lymph node. Ultrasound-guided percutaneous biopsy revealed metastatic poorly differentiated carcinoma. Histopathological examination could not conclusively distinguish between adenocarcinoma and squamous cell carcinoma. She was diagnosed with seronegative opsoclonus-myoclonus ataxia syndrome of paraneoplastic origin from an occult primary malignancy and started on pulsatile corticosteroids and intravenous immunoglobulin (IVIG), with only moderate symptomatic improvement. Given the anatomic location and immunohistochemical staining pattern of the lymph node, the malignancy was considered as being of primary breast origin. A left axillary lymph node dissection was performed, with 1/12 nodes testing positive for poorly differentiated carcinoma. The patient experienced significant improvement in her neurological symptoms 2–3 days following resection of the solitary malignant lymph node, largely regaining her functional independence. She went on to receive adjuvant radiotherapy to the breast and axilla, as well as adjuvant hormonal therapy. Full article
(This article belongs to the Section Surgical Oncology)
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11 pages, 5295 KiB  
Article
Primary Cardiac Tumors: Clinical Presentations and Pathological Features in a Multicenter Cohort
by Esra Çobankent Aytekin, Kemal Behzatoğlu, Arzu Akçay, Ayşe Özgün Şahin, Naile Kökbudak, Fahriye Kılınç, Aylin Okçu Heper, Olcay Kurtulan, Gülay Özbilim, Reyhan Eğilmez, Tülay Koç, Doğuş Özdemir Kara, Elif Ocak, Ali Aköz and İrem Hicran Özbudak
Diagnostics 2025, 15(15), 1951; https://doi.org/10.3390/diagnostics15151951 - 4 Aug 2025
Viewed by 132
Abstract
Background: Cardiac tumors are rare neoplasms with a wide spectrum of clinical presentations, ranging from asymptomatic cases to fatal outcomes. According to the 2021 thoracic tumor classification of the World Health Organization (WHO), papillary fibroelastoma (PFE) is the most common primary cardiac tumor. [...] Read more.
Background: Cardiac tumors are rare neoplasms with a wide spectrum of clinical presentations, ranging from asymptomatic cases to fatal outcomes. According to the 2021 thoracic tumor classification of the World Health Organization (WHO), papillary fibroelastoma (PFE) is the most common primary cardiac tumor. This study aimed to aggregate and examine data regarding the prevalence, clinical characteristics, and histological results of cardiac tumors. Methods: This multicenter retrospective study was conducted across seven tertiary care institutions and included 274 patients diagnosed with histopathologically confirmed cardiac tumors between January 2013 and December 2024. Results: This study included 274 patients, with an average age of 52.6 ± 16.6 years. Of the study participants, 120 (43.8%) were male and 154 (56.2%) were female. The most prevalent clinical manifestations were dyspnea (43.7%), thoracic pain (22.5%), and cardiac palpitations (21.1%). Echocardiography was the principal diagnostic method, revealing an average tumor size of 3 cm. The most commonly observed mass was cardiac myxoma (CM) in 192 patients (70.1%). The second most frequently detected mass was PFE (28 cases, 10.2%). The third most common cardiac mass was a metastatic tumor (6.9%). Surgical resection was performed in all patients, with infection being the most prevalent consequence, followed by effusion. Conclusions: Cardiac tumors, albeit uncommon, provide considerable diagnostic and treatment difficulties. Our research is founded on an extensive case series that has been histopathologically validated and sourced from various national tertiary centers. This comprehensive dataset offers epidemiological and clinical insights regarding heart tumors in Turkey. Another key finding of our study is that, even though the 5th edition of the 2021 WHO Classification of Thoracic Tumors lists PFE as the most common primary cardiac tumor, myxoma is actually the most common primary cardiac tumor in our study and in many other studies. This finding demonstrates a significant discrepancy between the current international classification and real-world data and suggests that tumor distribution may be related to regional and demographic differences. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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17 pages, 1907 KiB  
Systematic Review
Pilomatricoma in Syndromic Contexts: A Literature Review and a Report of a Case in Apert Syndrome
by Gianmarco Saponaro, Elisa De Paolis, Mattia Todaro, Francesca Azzuni, Giulio Gasparini, Antonio Bosso, Giuliano Ascani, Angelo Minucci and Alessandro Moro
Dermatopathology 2025, 12(3), 24; https://doi.org/10.3390/dermatopathology12030024 - 1 Aug 2025
Viewed by 180
Abstract
Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos [...] Read more.
Pilomatricomas are benign tumors originating from hair follicle matrix cells and represent the most common skin tumors in pediatric patients. Pilomatricomas may be associated with genetic syndromes such as myotonic dystrophy, familial adenomatous polyposis (FAP), Turner syndrome, Rubinstein–Taybi syndrome, Kabuki syndrome, and Sotos syndrome. This study reviews the literature on pilomatricomas occurring in syndromic contexts and presents a novel case linked to Apert syndrome. A systematic review was conducted using PubMed and Cochrane databases, focusing on case reports, case series, and reviews describing pilomatricomas associated with syndromes. A total of 1272 articles were initially screened; after removing duplicates and excluding articles without syndromic diagnoses or lacking sufficient data, 81 full-text articles were reviewed. Overall, 96 cases of pilomatricomas associated with genetic syndromes were identified. Reports of patients with Apert syndrome who do not develop pilomatricomas are absent in the literature. Pilomatricomas predominantly affect pediatric patients, with a slight female predominance, and are often the first manifestation of underlying genetic syndromes. Our study highlights previously unreported associations of pilomatricoma with Apert syndrome, providing molecular insights. This study contributes to understanding the clinical and molecular features of pilomatricomas in syndromic contexts and underscores the importance of genetic analysis for accurate diagnosis and management. Full article
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13 pages, 3428 KiB  
Review
Clinical and Demographics Aspects of Foot Angioleiomyomas: Case Reports and Systematic Review
by Antonio Córdoba-Fernández, Joaquín Mir-Gil, Carolina Díaz-Baena, Marina Ballesteros-Mora, Victoria Eugenia Córdoba-Jiménez and Aurora Castro-Méndez
Surgeries 2025, 6(3), 66; https://doi.org/10.3390/surgeries6030066 - 1 Aug 2025
Viewed by 149
Abstract
Background and Clinical Significance: Angioleiomyoma (ALM) is a benign tumor that generally presents as a single lesion and, according to the updated WHO classification, includes the following three histological subtypes: solid (or capillary), cavernous, and venous. Typically, ALMs are described as well-defined nodules [...] Read more.
Background and Clinical Significance: Angioleiomyoma (ALM) is a benign tumor that generally presents as a single lesion and, according to the updated WHO classification, includes the following three histological subtypes: solid (or capillary), cavernous, and venous. Typically, ALMs are described as well-defined nodules in the lower extremities but are unusually located in the acral locations and toes. We summarize two cases of ALM and perform a systematic review to provide foot surgeons with the most up-to-date and useful information on the epidemiological aspects, anatomical distribution, and specific histological subtypes of ALM in the foot. Materials and Methods: A systematic review was carried out according to the criteria of a PICO framework, and a systematic search and data processing were carried out according to the PRISMA guidelines. We analyzed patient demographics, clinical characteristics, diagnostic workup, treatment, and clinical outcomes. Each one of the included articles was independently assessed for methodological quality and risk of bias by an independent evaluator. The risk of bias of the included studies was assessed based on their characteristics. Results: This systematic review included 14 case series with 172 reported cases of ALM. One hundred and seventy-two (18.57%) were cases of ALM located on foot, excluding the ankle region. The female-to-male ratio was 1.48. The most common location was the hindfoot (41.5%), followed by the forefoot (20.2%) and the midfoot (8.9%). In 29.4% of cases, the location of the lesions could not be determined. The most frequent location of the lesions was subcutaneous (69%), followed by subaponeurotic (16.5%) and skin (14.5%) locations. The most frequent histological presentation was the solid histologic subtype (65%), followed by the venous subtype (21%) and the cavernous subtype (14%), respectively. Of the total reported cases of ALM located in foot, 63.1% presented as solid painful lesions. Calcified presentations occurred in 7% of cases, with more than half of the cases located in the hindfoot. Surgical excision was the treatment of choice in the two herein reported cases of solid ALM located in the hindfoot, one of them with a calcified presentation. No recurrence was observed in either case after two and five years of follow-up, respectively. All cases reviewed after surgical excision showed a low recurrence rate with a favorable prognosis regardless of the histological subtype and a very rare tendency toward malignancy. Conclusions: ALMs of the foot present as well-defined, painful nodules in the subcutaneous tissue of middle-aged women. Solid histological subtypes are the most prevalent. Histopathological analysis is usually essential for confirmation. Treatment consists primarily of direct excision, with remarkably low recurrence rates. Full article
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8 pages, 2841 KiB  
Case Report
Melanotrichoblastoma: A Histopathological Case Report of a Rare Pigmented Variant of Trichoblastoma
by George S. Stoyanov, Ivaylo Balabanov, Svetoslava Zhivkova and Hristo Popov
Reports 2025, 8(3), 130; https://doi.org/10.3390/reports8030130 - 1 Aug 2025
Viewed by 85
Abstract
Background and clinical significance: Trichoblastomas are rare, mixed epithelial tumors with a mesenchymal component and hair follicle differentiation. Case presentation: Herein, we present a case report of a 51-year-old female patient presenting to the obstetrics and gynecology department with complaints of edema and [...] Read more.
Background and clinical significance: Trichoblastomas are rare, mixed epithelial tumors with a mesenchymal component and hair follicle differentiation. Case presentation: Herein, we present a case report of a 51-year-old female patient presenting to the obstetrics and gynecology department with complaints of edema and erythema of the right Bartholin gland, and a lesion measuring 2 cm on the right lateral edge of the mons pubis, towards the inguinal fold. Marsupialization of the Bartholin gland was performed, as well as an incision into the pubo-inguinal lesion, which the patient depicted as grossly resembling an ingrown hair. Upon incision into the pubic–inguinal lesion, it was dark brown in color and spontaneously popped out of the subcutis, without an attempt at enucleation. Histology and subsequent immunohistochemistry of the lesion showed a blue basaloid tumor with an extensive pigment component located deep in the dermis that was sharply demarcated from the surrounding tissues. Conclusion: Immunohistochemistry was diffusely and strongly positive for epithelial markers; melanocytic markers were positive only in dendritic melanocytes dispersed within the tumors, and the proliferative index was low. As such, the tumor was identified as melanotrichoblastoma. Full article
(This article belongs to the Section Dermatology)
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20 pages, 2382 KiB  
Article
The Impact of the Injected Mass of the Gastrin-Releasing Peptide Receptor Antagonist on Uptake in Breast Cancer: Lessons from a Phase I Trial of [99mTc]Tc-DB8
by Olga Bragina, Vladimir Chernov, Mariia Larkina, Ruslan Varvashenya, Roman Zelchan, Anna Medvedeva, Anastasiya Ivanova, Liubov Tashireva, Theodosia Maina, Berthold A. Nock, Panagiotis Kanellopoulos, Jens Sörensen, Anna Orlova and Vladimir Tolmachev
Pharmaceutics 2025, 17(8), 1000; https://doi.org/10.3390/pharmaceutics17081000 - 31 Jul 2025
Viewed by 549
Abstract
Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific [...] Read more.
Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [99mTc]Tc-DB8 at a 80 µg DB8 dose (SUVmax 5.3 ± 1.2). Injection of [99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUVmax 2.0 ± 0.3) or 120 µg (SUVmax 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUVmax 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article
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12 pages, 643 KiB  
Article
Minimally Invasive Total Versus Partial Thymectomy for Early-Stage Thymoma
by Alexander Pohlman, Bilal Odeh, Irene Helenowski, Julia M. Coughlin, Wissam Raad, James Lubawski and Zaid M. Abdelsattar
Cancers 2025, 17(15), 2518; https://doi.org/10.3390/cancers17152518 - 30 Jul 2025
Viewed by 274
Abstract
Background/Objectives: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following [...] Read more.
Background/Objectives: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following total vs. partial thymectomy for early-stage thymoma. Methods: We identified patients diagnosed with WHO types A–B3 thymoma between 2010–2021 from a national hospital-based dataset. We excluded patients with stage II or higher disease, open resections and perioperative chemo-/radiation therapy. We stratified patients into total and partial thymectomy cohorts. We used propensity score matching to minimize confounding, Kaplan–Meier analysis to estimate survival, and Cox proportional hazards to identify associations. Results: Of 1598 patients with early-stage thymoma, 495 (31.0%) underwent partial and 1103 (69.0%) total thymectomy. Patients undergoing partial thymectomy were similar in sex (female 53.7% vs. 53.4%; p = 0.914), race (white 74.5% vs. 74.0%; p = 0.921), comorbidities (0 in 77.0% vs. 75.5%; p = 0.742), and tumor size (48.7 mm vs. 50.4 mm; p = 0.455) compared to total thymectomy. There were no differences in 30-day (0.8% vs. 0.6%, p = 0.747) or 90-day mortality (0.8% vs. 0.8%, p > 0.999), which persisted after matching. Moreover, 10-year survival was similar in both unmatched (p = 0.471) and matched cohorts (p = 0.828). Partial thymectomy was not independently associated with survival (aHR = 1.00, p = 0.976). Conclusions: In patients with early-stage thymoma, partial and total thymectomy were associated with similar short- and long-term outcomes. In light of recent attention to the role of the thymus gland, the results add important insights to shared decision-making discussions. Full article
(This article belongs to the Special Issue Advancements in Lung Cancer Surgical Treatment and Prognosis)
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15 pages, 4667 KiB  
Article
Longitudinal High-Resolution Imaging of Retinal Sequelae of a Choroidal Nevus
by Kaitlyn A. Sapoznik, Stephen A. Burns, Todd D. Peabody, Lucie Sawides, Brittany R. Walker and Thomas J. Gast
Diagnostics 2025, 15(15), 1904; https://doi.org/10.3390/diagnostics15151904 - 29 Jul 2025
Viewed by 258
Abstract
Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography [...] Read more.
Background: Choroidal nevi are common, benign tumors. These tumors rarely cause adverse retinal sequalae, but when they do, they can lead to disruption of the outer retina and vision loss. In this paper, we used high-resolution retinal imaging modalities, optical coherence tomography (OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO), to longitudinally monitor retinal sequelae of a submacular choroidal nevus. Methods: A 31-year-old female with a high-risk choroidal nevus resulting in subretinal fluid (SRF) and a 30-year-old control subject were longitudinally imaged with AOSLO and OCT in this study over 18 and 22 months. Regions of interest (ROI) including the macular region (where SRF was present) and the site of laser photocoagulation were imaged repeatedly over time. The depth of SRF in a discrete ROI was quantified with OCT and AOSLO images were assessed for visualization of photoreceptors and retinal pigmented epithelium (RPE). Cell-like structures that infiltrated the site of laser photocoagulation were measured and their count was assessed over time. In the control subject, images were assessed for RPE visualization and the presence and stability of cell-like structures. Results: We demonstrate that AOSLO can be used to assess cellular-level changes at small ROIs in the retina over time. We show the response of the retina to SRF and laser photocoagulation. We demonstrate that the RPE can be visualized when SRF is present, which does not appear to depend on the height of retinal elevation. We also demonstrate that cell-like structures, presumably immune cells, are present within and adjacent to areas of SRF on both OCT and AOSLO, and that similar cell-like structures infiltrate areas of retinal laser photocoagulation. Conclusions: Our study demonstrates that dynamic, cellular-level retinal responses to SRF and laser photocoagulation can be monitored over time with AOSLO in living humans. Many retinal conditions exhibit similar retinal findings and laser photocoagulation is also indicated in numerous retinal conditions. AOSLO imaging may provide future opportunities to better understand the clinical implications of such responses in vivo. Full article
(This article belongs to the Special Issue High-Resolution Retinal Imaging: Hot Topics and Recent Developments)
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27 pages, 5430 KiB  
Article
Gene Monitoring in Obesity-Induced Metabolic Dysfunction in Rats: Preclinical Data on Breast Neoplasia Initiation
by Francisco Claro, Joseane Morari, Camila de Angelis, Emerielle Cristine Vanzela, Wandir Antonio Schiozer, Lício Velloso and Luis Otavio Zanatta Sarian
Int. J. Mol. Sci. 2025, 26(15), 7296; https://doi.org/10.3390/ijms26157296 - 28 Jul 2025
Viewed by 310
Abstract
Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to [...] Read more.
Obesity and metabolic dysfunction are established risk factors for luminal breast cancer, yet current preclinical models inadequately recapitulate the complex metabolic and immune interactions driving tumorigenesis. To develop and characterize an immunocompetent rat model of luminal breast cancer induced by chronic exposure to a cafeteria diet mimicking Western obesogenic nutrition, female rats were fed a cafeteria diet or standard chow from weaning. Metabolic parameters, plasma biomarkers (including leptin, insulin, IGF-1, adiponectin, and estrone), mammary gland histology, tumor incidence, and gene expression profiles were longitudinally evaluated. Gene expression was assessed by PCR arrays and qPCR. A subgroup underwent dietary reversal to assess the reversibility of molecular alterations. Cafeteria diet induced significant obesity (mean weight 426.76 g vs. 263.09 g controls, p < 0.001) and increased leptin levels without altering insulin, IGF-1, or inflammatory markers. Histological analysis showed increased ductal ectasia and benign lesions, with earlier fibroadenoma and luminal carcinoma development in diet-fed rats. Tumors exhibited luminal phenotype, low Ki67, and elevated PAI-1 expression. Gene expression alterations were time point specific and revealed early downregulation of ID1 and COX2, followed by upregulation of MMP2, THBS1, TWIST1, and PAI-1. Short-term dietary reversal normalized several gene expression changes. Overall tumor incidence was modest (~12%), reflecting early tumor-promoting microenvironmental changes rather than aggressive carcinogenesis. This immunocompetent cafeteria diet rat model recapitulates key metabolic, histological, and molecular features of obesity-associated luminal breast cancer and offers a valuable platform for studying early tumorigenic mechanisms and prevention strategies without carcinogen-induced confounders. Full article
(This article belongs to the Special Issue Genomic Research in Carcinogenesis, Cancer Progression and Recurrence)
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26 pages, 7715 KiB  
Article
Harnessing Nature’s Chemistry: Deciphering Olive Oil Phenolics for the Control of Invasive Breast Carcinoma
by Nehal A. Ahmed, Abu Bakar Siddique, Afsana Tajmim, Judy Ann King and Khalid A. El Sayed
Molecules 2025, 30(15), 3157; https://doi.org/10.3390/molecules30153157 - 28 Jul 2025
Viewed by 387
Abstract
Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics [...] Read more.
Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article
(This article belongs to the Special Issue Bioactive Molecules in Foods: From Sources to Functional Applications)
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20 pages, 6787 KiB  
Article
PKC-ι Regulates an Oncogenic Positive Feedback Loop Between the MAPK/JNK Signaling Pathway, c-Jun/AP-1 and TNF-α in Breast Cancer
by Nuzhat Nowshin Oishee, Mahfuza Marzan, Abigail Oluwafisayo Olatunji, Khandker Mohammad Khalid, Abiral Hasib Shourav, Radwan Ebna Noor, Anna Kharitonova, Aaron Joshua Astalos, James W. Leahy and Mildred Acevedo-Duncan
Int. J. Mol. Sci. 2025, 26(15), 7288; https://doi.org/10.3390/ijms26157288 - 28 Jul 2025
Viewed by 353
Abstract
Breast cancer is the second most common cancer in the United States and consists of 30% of all new female cancer each year. PKC iota (PKC-ι) is a bonafide human oncogene and is overexpressed in many types of cancer, including breast [...] Read more.
Breast cancer is the second most common cancer in the United States and consists of 30% of all new female cancer each year. PKC iota (PKC-ι) is a bonafide human oncogene and is overexpressed in many types of cancer, including breast cancer. This study explores the role of PKC-ι in regulating the transcription factor Jun proto-oncogene (c-Jun), pro-inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α), and the Mitogen-Activated Protein Kinase/Jun N-terminal kinase (MAPK/JNK) pathway, which also exhibits an oncogenic role in breast cancer. ICA-1S, a PKC-ι specific inhibitor, was used to inhibit PKC-ι to observe the subsequent effect on the levels of c-Jun, TNF-α, and the MAPK/JNK signaling pathway. To obtain the results, cell proliferation assay, Western blotting, co-immunoprecipitation, small interfering RNA (siRNA), immunofluorescence, flow cytometry, cycloheximide (CHX) chase assay, and reverse transcription quantitative PCR (RT-qPCR) techniques were implemented. ICA-1S significantly inhibited cell proliferation and induced apoptosis in both breast cancer cell lines. Treatment with ICA-1S and siRNA also reduced the expression levels of the MAPK/JNK pathway protein, c-Jun, and TNF-α in both cell lines. PKC-ι was also found to be strongly associated with c-Jun, via which it regulated the MAPK/JNK pathway. Additionally, ICA-1S was found to promote the degradation of c-Jun and decrease the mRNA levels of c-Jun. We concluded that PKC-ι plays a crucial role in regulating breast cancer, and the inhibition of PKC-ι by ICA-1S reduces breast cancer cell proliferation and induces apoptosis. Therefore, targeting PKC-ι as a potential therapeutic target in breast cancer could be a significant approach in breast cancer research. Full article
(This article belongs to the Special Issue Molecular Research and Cellular Biology of Breast Cancer)
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12 pages, 2409 KiB  
Review
Tumors of the Parapharyngeal Space Presenting with Obstructive Sleep Apnea: A Case Report and Literature Review
by Luca Cerri, Francesco Giombi, Michele Cerasuolo, Gian Marco Pace, Anna Losurdo, Giuseppe Lunardi, Francesco Grecchi, Elena Volpini and Luca Malvezzi
J. Pers. Med. 2025, 15(8), 331; https://doi.org/10.3390/jpm15080331 - 28 Jul 2025
Viewed by 287
Abstract
Introduction: Obstructive sleep apnea syndrome (OSAS) is caused by anatomical and non-anatomical factors which lead to upper airway (UA) obstruction during sleep. Intrinsic UA collapse is the most frequent determinant of OSA. In the era of personalized medicine, adopting a tailored diagnostic [...] Read more.
Introduction: Obstructive sleep apnea syndrome (OSAS) is caused by anatomical and non-anatomical factors which lead to upper airway (UA) obstruction during sleep. Intrinsic UA collapse is the most frequent determinant of OSA. In the era of personalized medicine, adopting a tailored diagnostic approach is essential to rule out secondary causes of UA collapse, particularly those stemming from extrinsic anatomical factors. Although being rarely considered in the differential diagnosis, space-occupying lesions of deep cervical spaces such as the parapharyngeal space (PPS) may be responsible for airway obstruction and lead to OSAS. Objective: This study aimed to present an atypical case of OSAS caused by extrinsic PPS compression, outlining the relevance of modern personalized medicine in the diagnostic and therapeutic protocols, and to enhance understanding through a comprehensive literature review. Methods: A 60-year-old female presented with sleep-disordered complaints and was diagnosed with severe OSAS after polysomnography. At physical examination, a swelling of the right posterior oropharyngeal mucosa was noticed. Imaging confirmed the suspicion of a PPS tumor, and transcervical resection was planned. Case presentation was adherent to the CARE checklist. A comprehensive literature review was conducted using the most reliable scientific databases. Results: Surgery was uneventful, and the patient made a full recovery. The histopathology report was consistent with the diagnosis of pleomorphic adenoma. Postoperative outcomes showed marked improvement in polysomnographic parameters and symptom burden. Conclusions: Parapharyngeal space tumors are a rare, often overlooked cause of OSA. This case highlights the role of a personalized head and neck assessment in OSA patients, particularly in identifying structural causes and offering definitive surgical management when indicated. Full article
(This article belongs to the Section Personalized Therapy and Drug Delivery)
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14 pages, 1588 KiB  
Article
Ageing and BMI in Focus: Rethinking Risk Assessment for Vertebral Fragility and Pedicle Screw Loosening in Older Adults
by Jun Li, André Strahl, Beate Kunze, Stefan Krebs, Martin Stangenberg, Lennart Viezens, Patrick Strube and Marc Dreimann
J. Clin. Med. 2025, 14(15), 5296; https://doi.org/10.3390/jcm14155296 - 27 Jul 2025
Viewed by 491
Abstract
Background/Objectives: Pathological vertebral fragility (path-VF) increases the risk of osteoporotic fractures and pedicle screw loosening (PSL) after posterior instrumented spinal fusion (PISF). While WHO body mass index (BMI) categories broadly identify risks related to underweight and obesity, fixed thresholds may inadequately reflect [...] Read more.
Background/Objectives: Pathological vertebral fragility (path-VF) increases the risk of osteoporotic fractures and pedicle screw loosening (PSL) after posterior instrumented spinal fusion (PISF). While WHO body mass index (BMI) categories broadly identify risks related to underweight and obesity, fixed thresholds may inadequately reflect vertebral fragility risks among elderly patients, especially within the normal-weight range. This study investigates whether current BMI classifications sufficiently capture the risk of path-VF in older adults. Methods: This retrospective study included 225 patients who underwent kyphoplasty or PISF (2022–2023). Path-VF was defined by non-tumorous fractures, screw reinforcement, or PSL within six months without prior reinforcement. Patients were grouped into the path-VF (n = 94) and control (n = 131) groups. HU and BMI values, BMI-related ORs, and age trends were analysed, and a logistic regression was performed. Results: Mean HU values were significantly lower in the path-VF group (71.37 ± 30.50) than in controls (130.35 ± 52.53, p < 0.001). Path-VF females (26.26 ± 5.38) had a lower BMI than the control females (29.33 ± 5.98, p = 0.002); no difference was found in males. Normal-weight females showed a borderline risk for path-VF (OR 2.03, p = 0.0495). Obesity (ORmale 0.31/ORfemale 0.37) and being male and overweight (OR 0.21) were protective (all p < 0.05). BMI declined with age in path-VF males (p = 0.001) but increased in the controls (p = 0.023). A logistic regression identified a BMI < 22.5 kg/m2 and age > 67.5 years as significant risk thresholds. Notably, 20.2% of path-VF patients over 67.5 had a normal weight, suggesting a potentially overlooked subgroup. Conclusions: The current WHO lower limit for normal BMI (18.5 kg/m2) may underestimate the risk of path-VF in patients older than 67.5 years, potentially overlooking 24.7% of cases. The results offer a new approach for clinicians to interpret BMI values at the lower end of the normal range (<22.5 kg/m2) with caution in elderly patients undergoing spinal surgery. Full article
(This article belongs to the Special Issue Current Progress and Future Directions of Spine Surgery)
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