Tumor Metastatic Potential Research Articles

Regulation of Oxygen in the Tumor Microenvironment Synergizes with Immunotherapy to Suppress Tumor Progression

Hypoxia represents a crucial characteristic of the tumor microenvironment, which is closely related to cell proliferation, angiogenesis, and metabolic responses. These factors will further promote tumor progression, increase tumor invasion, and enhance tumor metastasis potential. A hypoxic microenvironment will also inhibit the activity of infiltrated immune cells in the tumor microenvironment, leading to the failure of cancer immunotherapy. Additionally, the hypoxic tumor microenvironment contributes to resistance to conventional therapies and leads to unfavorable prognoses. This review discusses advancements in strategies aimed at ameliorating tumor hypoxia within the microenvironment and modulating immune cell responses against tumors.

The Use of Near-Infrared Indocyanine Green Fluorescence Imaging to Differentiate Benign Versus Malignant Adrenal Tumors.

Despite advances in imaging modalities, a significant number of adrenal tumors are considered indeterminate and removed surgically. Currently, there is no intraoperative tool available to provide further information about the nature of indeterminate adrenal tumors. The aim of this study was to investigate whether near-infrared indocyanine green (ICG) imaging can be used in this regard. This was an institutional review board-approved study. Within 9 years, 197 patients underwent robotic adrenalectomy with ICG imaging. Adrenal tumors were characterized prospectively as fluorescent or nonfluorescent intraoperatively. ICG was administered as a 2.5 mg dose, one to three times a procedure. No patient developed an allergic reaction. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Robotic transabdominal lateral adrenalectomy was performed in 155 patients and posterior retroperitoneal adrenalectomy in 42 patients. One hundred and eighty-four patients had benign adrenal tumors, 10 patients had malignant tumors, and three patients had tumors of uncertain malignant potential. Sensitivity, specificity, PPV, and NPV to predict a benign tumor were 87%, 38.5%, 95.2%, and 17.2%. To our knowledge, this is the largest study on ICG imaging of adrenal tumors. High PPV to detect benign tumors suggests a utility of ICG to provide the surgeon with further information about the benign vs malignant nature of indeterminate adrenal tumors taken to surgery.

Label-Free Prediction of Tumor Metastatic Potential via Ramanome.

Assessing metastatic potential is crucial for cancer treatment strategies. However, current methods are time-consuming, labor-intensive, and have limited sample accessibility. Therefore, this study aims to investigate the urgent need for rapid and accurate approaches by proposing a Ramanome-based metastasis index (RMI) using machine learning of single-cell Raman spectra to rapidly and accurately assess tumor cell metastatic potential. Validation with various cultured tumor cells and a mouse orthotopic model of pancreatic ductal adenocarcinoma show a Kendall rank correlation coefficient of 1 compared to Transwell experiments and histopathological assessments. Significantly, lipid-related Raman peaks are most influential in determining RMI. The lipidomic analysis confirmed strong correlations between metastatic potential and phosphatidylcholine, phosphatidylethanolamine, cholesteryl ester, ceramide, and bis(monoacylglycero)phosphate, crucial in cell membrane composition or signal transduction. Therefore, RMI is a valuable tool for predicting tumor metastatic potential and providing insights into metastasis mechanisms.

Evidence that CRISPR-Cas9 Y537S-mutant expressing breast cancer cells activate Yes-associated protein 1 to driving the conversion of normal fibroblasts into cancer-associated fibroblasts

BackgroundEndocrine therapy (ET) has improved the clinical outcomes of Estrogen receptor alpha-positive (ERɑ +) breast cancer (BC) patients, even though resistance to ET remains a clinical issue. Mutations in the hormone-binding domain of ERɑ represent an acquired intrinsic mechanism of ET resistance. However, the latter also depends on the multiple functional interactions between BC cells and the tumor microenvironment (TME). Here, we investigated how the most common Y537S-ERɑ mutation may influence the behavior of fibroblasts, the most prominent component of the TME.MethodsWe conducted coculture experiments with normal human foreskin fibroblasts BJ1-hTERT (NFs), cancer-associated fibroblasts (CAFs), isolated from human BC specimens, and Y537S CRISPR-expressing MCF-7 BC cells (MCF-7YS). Mass spectrometry (MS) and Metacore analyses were performed to investigate how the functional interactions between BC cells/fibroblasts may affect their proteomic profile. The impact of fibroblasts on BC tumor growth and metastatic potential was evaluated in nude mice.ResultsMutant BC conditioned medium (CM) affected the morphology/proliferation/migration of both NFs and CAFs. 198 deregulated proteins signed the proteomic similarity profile of NFs exposed to the YS-CM and CAFs. Among the upregulated proteins, Yes-associated protein 1 (YAP1) was the main central hub in the direct interaction network. Increased YAP1 protein expression and activity were confirmed in NFs treated with MCF-7YS-CM. However, YAP1 activation appears to crosstalk with the insulin growth factor-1 receptor (IGF-1R). Higher amount of IGF-1 were noticed in the MCF-7YS-CM cells compared to the MCF-7P, and IGF-1 immunodepletion reversed the enhanced YAP1 expression and activity. Mutant cells upon exposure to the NF- and CAF-CM exhibited an enhanced proliferation/growth/migration/invasion compared to the MCF-7P. MCF-7YS cells when implanted with CAFs showed an early relative increased tumor volume compared to YS alone. No changes were observed when MCF-7P cells were co-implanted with CAFs. Compared with that in MCF-7P cells, the metastatic burden of MCF-7YS cells was intrinsically greater, and this effect was augmented upon treatment with NF-CM and further increased with CAF-CM.ConclusionsYS mutant BC cells induced the conversion of fibroblasts into CAFs, via YAP, which represent a potential therapeutic target which interrupt the functional interactions between mutant cells/TME and to be implemented in the novel therapeutic strategy of a subset of metastatic BC patients carrying the frequent Y537S mutations.

Abstract PR002: The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients

Abstract Circulating tumor cells (CTCs) play a critical role in the metastatic process of cancer and are widely recognized as important biomarkers that provide valuable information related to tumor characteristics. While most research to date has focused on the biological markers and molecular properties of CTCs, their physical characteristics, particularly size, have been relatively underexplored. However, recent studies suggest that smaller CTCs exhibit enhanced tumor- initiating and metastatic abilities compared to larger CTCs. This indicates that CTC size is not merely a physical trait but may directly influence the invasiveness and metastatic potential of tumors. Such findings suggest that CTC size could be an important indicator for predicting tumor malignancy and provide a new perspective on understanding cancer progression and metastasis. As such, there is a growing emphasis on research that considers the size of CTCs. In this study, it was speculated whether CTC size holds clinical significance in patients with head and neck squamous cell carcinoma (HNSCC). The study was involved with 20 HNSCC patients, analyzing the morphological characteristics of CTCs collected from blood samples before and after treatment, while exploring the potential for monitoring treatment response. Our results found that CTCs were detected 20% more frequently in oropharyngeal cancer (OPC) patients compared to non-OPC patients. This is likely due to the rich vascularity in the oropharyngeal region, which may facilitate greater entry of CTCs into the bloodstream. Additionally, the cell size (23.9 μm in average) and nuclear size (16.4 μm in average) of HPV-positive patients were 32% and 10% larger, respectively, than those of HPV-negative patients (cell size: 18.1 μm; nuclear size: 12.60 μm). This suggests that the sizes of CTC and their nuclei may be associated with HPV status, which is presumed to be due to HPV causing disruptions in the cell cycle. In addition, we could successfully cultivate the CTCs obtained from HPV-positive patients with relatively smaller CTCs for 30 days, predicting that small CTCs have affordable for CTC culture. In conclusion, this study confirms that the physical characteristics of CTCs, particularly size, are linked to HPV infection status in HNSCC patients. CTC- and nucleus- size are closely related to tumor characteristics, demonstrating the potential for developing diagnostic and prognostic tools based on these physical traits. Although more in-depth research is required, poor prognosis in HPV- positive patients may also be related to the physical characteristics of CTCs. Citation Format: Hyeongjung Woo, Hyun Young Shin, So Yeon Oh, Sun Min Lee, Minseok S. Kim. The clinical relevance of circulating tumor cell size in head and neck squamous cell carcinoma patients [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR002.

011. Solid-Pseudopallary Tumor of Pancreas in Childhood, A Case Report

Background: Solid-pseudopapillary tumor of the pancreas (SPT) is an exceptionally rare neoplasm in children. Its origin remains enigmatic. It occurs most frequently in young females within the second or third decade of life with only a small minority concerning children. Frequently described as low malignant potential tumors, surgical resection remains the main treatment. Case: The authors present a case of a SPT diagnosed in a 12-year-old with vomiting and abdominal pain localized to the right upper quadrant 2 week before admission to hospital. The patient also became yellowish since 1 week before. The patient undergo MRI scans and showed the presence Heterogeneous solid mass with components of necrosis and bleeding in it in the head of the pancreas. The patient undergone surgery with the histomorphology result Solid Pseudopapillary Neoplasm of pancreas, low grade malignancy. Conclusion: SPT is a rare differential diagnosis of a pancreatic mass in children. It is mandatory to establish this diagnosis since complete surgical removal of the tumor even in case of metastases or local invasion offers an excellent prognosis

Experimental and in silico analysis of LINC01279 expression in tumor of patients with breast cancer.

Breast cancer (BC) is characterized by the increase of malignant cells in the breast. The malignant cells begin in the lining of the breast milk glands or ducts (ductal epithelium). BC is the most frequent cancer in women, but it may also occur in males. Long non-coding RNAs (lncRNA) have been demonstrated to control the development and incidence of cancer. However, some lncRNAs experience potential changes in BC, but their role has not been well studied. LINC01279 is known as a valuable biomarker in gastric cancer but has not yet been studied in BC. Changes in LINC01279 expression levels in BC samples were investigated by microarray. Q-PCR was also used to evaluate the expression of LINC01279 in the tumor and normal adjacent samples of 30 BC patients. The LINC01279 co-expressed gene module was discovered using weighted gene correlation network analysis (WGCNA) on the relevant dataset. The top ten hub genes were determined using gene ontology (GO) functional enrichments on the co-expressed gene module. The results of the bioinformatics study showed an increase in LINC01279 expression levels (log2FC = 3.228749561, adj.P.Val = 1.69E - 12) in tumor samples compared to normal marginal tissue. Q-PCR results also showed a significant increase in LINC01279 expression (P-value = 0.0005) in tumor samples. WGCNA analysis identified that the black module is the LINC01279 co-expressed module, and functional annotation analysis of black module genes enriched in significant cancer-related pathways and processes, including cell growth and/or maintenance, regulation of immune response, regulation of cell proliferation, and epithelial-to-mesenchymal transition (EMT). Regarding the real-time PCR results, the analysis of expression patterns has illuminated a distinct association between the heightened expression levels of LINC01279, and the stages of cancer progression as well as the metastatic potential of tumors. However, intriguingly, our observations have failed to reveal any statistically significant correlations between the relative expression of LINC01279 and tumor grade classification, or the presence of ER, PR, and HER2 biomarkers. The present study could provide a new perspective on the molecular regulatory. Processes associated with BC pathogenic mechanisms are linked to the LINC01279, although further research is needed on the possible role of this lncRNA in BC.

Approaches to the Diagnosis and Management of Paediatric Ovarian Tumours and Oncological Outcomes in a Single-centre Study. Evidence in Support Of IPSO Reccomendations

BackgroundApproaches to paediatric ovarian tumours vary. Cross-sectional imaging is reliable but not always performed. Laparoscopic tumourectomy, although popular, is not recommended by International Paediatric Surgical Oncology Society (IPSO); tumour spillage remains the main concern. We aimed to investigate the reliability of preoperative evaluation and identify perioperative factors associated with adverse outcomes. MethodsSingle-centre retrospective study (2015–2022) of clinical presentation, preoperative investigation, operative approaches and oncological outcomes in all females <18 years treated for ovarian tumours. Logistic regression was used to identify predictors of malignancy and of second disease events. Data are presented as median (IQR) or rates. ResultsSixty girls aged 12.5 (10–15) years with follow-up of 51 (30.5–76.3) months were included. Incidence of malignant and low malignant potential tumours was 19/60 (32%). Tumour size and consistency proved predictive of malignancy. Clinical assessement, tumour markers and cross-sectional imaging combined showed 75% sensitivity, 100% specificity and 7% misclassified malignancy rate. Second disease events (11/60, 18%) were associated with misclassified malignancy (2/11 vs. 1/49, p = 0.04) and positive margins (4/11 vs. 5/49, p = 0.02). Ovarian-sparing surgery did not influence second events (5/11 vs. 28/49, p = 0.48). There was no significant association between second events and laparoscopic tumourectomy (3/11 vs. 20/49, p = 0.40); spillage rate was however more frequent with laparoscopy (5/11 vs. 2/32, p = 0.008). ConclusionMisclassified malignancy, noted in 7% of patients undergoing optimal work-up, adversely impacted outcomes, highlighting the importance of oncological principles in both oophorectomy and ovarian-sparing surgery. Malignancy incidence and misclassification can be underestimated when tumours with malignant behaviour potential, such as immature teratomas and borderline tumours, are grouped as benign. There was no direct association between operative approaches and second events. Laparoscopy, however, failed to maintain oncological principles more frequently than open surgery and hence risks upstaging of paediatric ovarian pathology. Level of evidenceIII.

Tumor Hypoxia and Radioresistance

Tumor hypoxia is a prevalent feature of solid tumors, significantly contributing to increased tumor aggressiveness, metastatic potential, and resistance to conventional therapies such as radiotherapy. This review explores the complex relationship between tumor hypoxia and radioresistance, highlighting the molecular mechanisms involved and potential therapeutic strategies to enhance radiotherapy efficacy in hypoxic tumors. Key mechanisms include the role of hypoxia-inducible factors (HIFs), particularly HIF-1α, which regulates numerous genes involved in tumor survival, proliferation, and resistance under hypoxic conditions. The review also discusses the oxygen enhancement ratio (OER) and its impact on radiotherapy outcomes, emphasizing how hypoxia leads to reduced radiosensitivity by limiting the formation of radiation-induced DNA damage. Despite the development of various strategies to counteract hypoxia-induced radioresistance, such as HIF inhibitors, hypoxia-targeted gene therapy, and hypoxia-activated prodrugs (HAPs), clinical results have been mixed, necessitating further research. Additionally, advances in imaging techniques for detecting tumor hypoxia are explored, which may allow for more personalized radiotherapy approaches, such as dose painting. The future of overcoming tumor hypoxia in radiotherapy lies in the integration of innovative therapeutic strategies, personalized medicine, and improved imaging technologies, offering hope for enhanced treatment outcomes in cancer patients.

From Spheroids to Bioprinting: A Literature Review on Biomanufacturing Strategies of 3D In Vitro Osteosarcoma Models

AbstractOsteosarcoma (OS) is a rare primary malignant bone cancer affecting mainly young individuals. Treatment typically consists of chemotherapy and surgical tumor resection, which has undergone few improvements since the 1970s. This therapeutic approach encounters several limitations attributed to the tumor's inherent chemoresistance, marked heterogeneity and metastatic potential. Therefore, the development of in vitro platforms that closely mimic the OS pathophysiology is crucial to understand tumor progression and discover effective anticancer therapeutics. Contrary to 2D monolayer cultures and animal models, 3D in vitro platforms show promise in replicating the 3D tumor macrostructure, cell‐cell and cell‐extracellular matrix interactions. This review provides an overview of the biomanufacturing strategies employed in developing 3D in vitro OS models, highlighting their role in replicating different aspects of OS and improving OS anticancer research and drug screening. A variety of 3D in vitro models are explored, including both scaffold‐free and scaffold‐based models, encompassing cell spheroids, hydrogels, and innovative approaches like electrospun nanofibers, microfluidic devices and bioprinted constructs. By examining the distinctive features of each model type, this review offers insights into their potential transformative impact on the landscape of OS research and therapeutic innovation, addressing the challenges and future directions of 3D in vitro OS modeling.

Evaluation and Surgical Management of Pediatric Cutaneous Melanoma and Atypical Spitz and Non-Spitz Melanocytic Tumors (Melanocytomas): A Report From Children's Oncology Group.

The purpose of this study was to develop recommendations for the diagnostic evaluation and surgical management of cutaneous melanoma (CM) and atypical Spitz tumors (AST) and non-Spitz melanocytic tumors (melanocytomas) in pediatric (age 0-10 years) and adolescent (age 11-18 years) patients. A Children's Oncology Group-led panel with external, multidisciplinary CM specialists convened to develop recommendations on the basis of available data and expertise. Thirty-three experts from multiple specialties (cutaneous/medical/surgical oncology, dermatology, and dermatopathology) established recommendations with supporting data from 87 peer-reviewed publications. (1) Excisional biopsies with 1-3 mm margins should be performed when feasible for clinically suspicious melanocytic neoplasms. (2) Definitive surgical treatment for CM, including wide local excision and sentinel lymph node biopsy (SLNB), should follow National Comprehensive Cancer Network Guidelines in the absence of data from pediatric-specific surgery trials and/or cohort studies. (3) Accurate classification of ASTs as benign or malignant is more likely with immunohistochemistry and next-generation sequencing. (4) It may not be possible to classify some ASTs as likely/definitively benign or malignant after clinicopathologic and/or molecular correlation, and these Spitz tumors of uncertain malignant potential should be excised with 5 mm margins. (5) ASTs favored to be benign should be excised with 1- to 3-mm margins if transected on biopsy. (6) Re-excision is not necessary if the AST does not extend to the biopsy margin(s) when complete/excisional biopsy was performed. (7) SLNB should not be performed for Spitz tumors unless a diagnosis of CM is favored on clinicopathologic evaluation. (8) Non-Spitz melanocytomas have a presumed increased risk for progression to CM and should be excised with 1- to 3-mm margins if transected on biopsy. (9) Re-excision of non-Spitz melanocytomas is not necessary if the lesion is completely excised on biopsy.

Common Diagnostic Challenges in Genitourinary Mesenchymal Tumors: A Practical Approach.

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls.

Estrogen receptors and extracellular matrix: the critical interplay in cancer development and progression.

Cancer remains a significant global health concern. Breast cancer is a multifaceted and prevalent disease influenced by several factors, among which estrogen receptors (ERs) and the extracellular matrix (ECM) play pivotal roles. ERs, encompassing ERα and ERβ, exert significant diversity on tumor behavior, cell signaling, invasion, and metastatic potential, thus guiding breast cancer prognosis. Understanding the multifunctional connections between ERs and ECM that mediate the dynamics of tumor microenvironment is vital for unraveling the complexity of breast cancer pathobiology and identifying novel therapeutic targets. This critical review delves into the intricate nature of ERs, emphasizing their structural isoforms and the consequential impact on breast cancer outcomes. A detailed examination of ER-mediated cell signaling pathways reveals how differential expression of ERα and ERβ isoforms influence breast cancer cell behavior. The functional ERs-matrix interactions emerge as a pivotal factor in modulating epigenetic mechanisms of breast cancer cells, orchestrating changes in cellular phenotype and expression patterns of matrix modulators. Specifically, ERα isoforms are shown to regulate ECM signaling cascades, while the effects of ECM components on ERα activity highlight a bidirectional regulatory axis. The diversity of ERβ isoforms is also highlighted, illustrating their distinct contribution to ECM-mediated cellular responses. This review underscores the complex interplay between ERα/β isoforms and the ECM, shedding light onto the potential therapeutic strategies targeting these interactions to improve breast cancer management.

Research on the biophysical properties of circulating tumor cells

This article reviews the biophysical properties of circulating tumor cells (CTCs) and their significance in tumor metastasis and liquid biopsy. CTCs are tumor cells that have shed from solid tumors or metastatic foci and entered the bloodstream, possessing various biological markers. They may be cleared by the immune system, enter a dormant state, or form clusters to facilitate metastasis. The physical properties of CTCs, including cell size, density, rigidity, and dielectric properties, differ from normal blood cells, providing a theoretical basis for separation and detection. The biological characteristics of CTCs include epithelial cell properties, expression of specific surface marker proteins, and the characteristics of epithelial-mesenchymal transition, which are crucial for the aggressiveness and metastatic potential of tumors. The development of CTC detection technologies, such as the Cell Search system, has been clinically applied, but the heterogeneity of tumor cells remains a major challenge in research. The development of composite separation technologies that combine various properties of CTCs is expected to improve the sensitivity, specificity, and efficiency of CTC detection, thereby playing an important role in the personalized treatment and prognostic assessment of tumors.

Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling.

Triple negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSCs), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets including NQO1. Here, we identified the antioxidant enzymes NQO1 and SOD1 as therapeutic vulnerabilities of ALDH+ epithelial-like CSCs and CD24-/loCD44+/hi mesenchymal-like CSCs in TNBC. Effective targeting of these CSC states was achieved by utilizing IB-DNQ, a potent and specific NQO1-bioactivatable futile redox cycling molecule, which generated large amounts of reactive oxygen species (ROS) including superoxide and hydrogen peroxide. Furthermore, the CSC killing effect was specifically enhanced by genetic or pharmacological inhibition of SOD1, a copper-containing superoxide dismutase highly expressed in TNBC. Mechanistically, a significant portion of NQO1 resided in the mitochondrial intermembrane space, catalyzing futile redox cycling from IB-DNQ to generate high levels of mitochondrial superoxide, and SOD1 inhibition markedly potentiated this effect resulting in mitochondrial oxidative injury, cytochrome c release, and activation of the caspase 3-mediated apoptotic pathway. Treatment with IB-DNQ alone or together with SOD1 inhibition effectively suppressed tumor growth, metastasis, and tumor-initiating potential in xenograft models of TNBC expressing different levels of NQO1. This futile oxidant-generating strategy, which targets CSCs across the epithelial-mesenchymal continuum, could be a promising therapeutic approach for treating TNBC patients.

Imaging characteristics of uterine smooth muscle tumors of uncertain malignant potential: a case report and literature review.

Uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are rare tumors of the uterine myometrium that are often misdiagnosed, owing to limited knowledge of their characteristics on ultrasonography (US) and magnetic resonance imaging (MRI). We report a woman in her mid-30s who was hospitalized because of a pelvic tumor. A 6-cm mass was found in her lower left abdomen. US and MRI revealed a well-demarcated mass in the left adnexal area, with both cystic and solid elements, visible blood flow within the septa, a strong signal across >50% of the volume on T2-weighted imaging (T2WI), and a strong signal on diffusion-weighted imaging (DWI). After hysterectomy and bilateral salpingectomy, immunohistochemical examination confirmed STUMP. A review of the literature revealed characteristic imaging features of STUMP. Ultrasonography reveals STUMP as a solitary, well-circumscribed lesion with isoechoic or mixed echogenicity, the absence of posterior shadowing, and variations in blood flow. STUMP is characterized by strong signal intensity on T2WI, small areas of strong signal on T1WI, and non-enhancing cystic areas on contrast-enhanced MRI scans. Early diagnosis is crucial for the management and treatment of STUMP, and here we have summarized the imaging features of the lesion, thereby providing a valuable diagnostic reference.

Smooth muscle tumors of uncertain malignant potential or atypical leiomyomas: A long-term evaluation of surgical outcomes and clinicopathological features

ObjectiveThe Primary Objective of this study was to analyse reproductive outcomes in patients with STUMP (Smooth Muscle Tumour of Uncertain Potential) or ALM (Atypical Leiomyoma) who underwent fertility-preserving surgeries. Secondary Objectives were to analyse long-term prognosis for these patients and to study the basic demographic and pathological characteristics of patients with STUMP or ALM. Study Design:This retrospective study was conducted at Amrita Institute of Medical Sciences. Cases of STUMP and ALM were retrieved from the hospital medical database between June 2014 and December 2022. Demographic parameters, clinical presentations, pathological features and clinical outcomes were analysed. Categorical variables were expressed in numbers and percentages. Normal distribution data were presented as mean while non-normal distribution was expressed as median and range. ResultsThirty-eight patients were included in the study with a diagnosis of STUMP or ALM in postoperative histology. Seven patients (18.4%) were nulliparous. Myomectomy was performed in 9 (23.6%), while hysterectomy was done in 29 patients (76.3%). Fertility-preserving surgeries were performed on six patients (15.7%). Of these six patients, 4(66.6%) conceived spontaneously and had successful pregnancies. Recurrences were found in 3 patients (7.8%) out of which one had undergone fertility-sparing surgery. All the patients with recurrences had previous history of myomectomies. Morcellation was reportedly done in 2 of these three patients. ConclusionGood reproductive outcomes have been demonstrated in patients diagnosed with STUMP or ALM and desiring fertility. However, these patients should be kept under follow-up care as they are prone for recurrences. Patients who have undergone morcellation mayhave an increased chance of recurrence.

The Anticancer Effects and Therapeutic Potential of Kaempferol in Triple-Negative Breast Cancer.

Breast cancer is the second-leading cause of cancer death among women in the United States. Triple-negative breast cancer (TNBC), a subtype of breast cancer, is an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which is challenging to treat with standardized hormonal therapy. Kaempferol is a natural flavonoid with antioxidant, anti-inflammatory, neuroprotective, and anticancer effects. Besides anti-tumorigenic, antiproliferative, and apoptotic effects, kaempferol protects non-cancerous cells. Kaempferol showed anti-breast cancer effects by inducing DNA damage and increasing caspase 3, caspase 9, and pAMT expression, modifying ROS production by Nrf2 modulation, inducing apoptosis by increasing cleaved PARP and Bax and downregulating Bcl-2 expression, inducing cell cycle arrest at the G2/M phase; inhibiting immune evasion by modulating the JAK-STAT3 pathway; and inhibiting the angiogenic and metastatic potential of tumors by downregulating MMP-3 and MMP-9 levels. Kaempferol holds promise for boosting the efficacy of anticancer agents, complementing their effects, or reversing developed chemoresistance. Exploring novel TNBC molecular targets with kaempferol could elucidate its mechanisms and identify strategies to overcome limitations for clinical application. This review summarizes the latest research on kaempferol's potential as an anti-TNBC agent, highlighting promising but underexplored molecular pathways and delivery challenges that warrant further investigation to achieve successful clinical translation.

A clinical ultrasound algorithm to identify uterine sarcoma and smooth muscle tumors of uncertain malignant potential in patients with myometrial lesions: the MYometrial Lesion UltrasouNd And mRi study

BackgroundDifferential diagnosis between benign uterine smooth muscle tumors and malignant counterpart is challenging. We evaluated the accuracy of a clinical and ultrasound based algorithm in predicting mesenchimal uterine malignancies (MUMs), including smooth muscle tumors of uncertain malignant potential (STUMPs). MethodsWe report the twelve-months follow-up of an observational, prospective, single-centre study that included women with at least one myometrial lesion ≥3 cm on ultrasound examination. These patients were classified according to a three-class diagnostic algorithm, using symptoms and ultrasound features. “White” patients underwent annual telephone follow-up for 2 years, “Green” patients underwent a clinical and ultrasound follow-up at 6, 12 and 24 months and “Orange” patients underwent surgery. We further developed a risk class system to stratify the malignancy risk. Findings2,268 women were included andtarget lesion was classified as benign in 2,158 (95.1%), as other malignancies in 58 (2.6%) an as mesenchymal uterine malignancies in 52 (2.3%) patients. At multivariable analysis, age (OR 1.05 (95% CI 1.03-1.07), tumor diameter >8 cm (OR 5.92 (95% CI 2.87-12.24), irregular margins (OR 2.34 (95% CI 1.09-4.98), color score=4 (OR 2.73 (95% CI 1.28-5.82), were identified as independent risk factors for malignancies, whereas acoustic shadow resulted in an independent protective factor (OR 0.39 (95% CI 0.19-0.82). The model, which included age as a continuous variable and lesion diameter as a dichotomized variable (cut-off 81 mm), provided the best AUC (0.87 (95% CI 0.82-0.91)). A risk class system was developed, and patients were classified as low-risk (predictive model value <0.39%: 0/606 malignancies, risk 0%), intermediate risk (predictive model value 0.40%-2.2%: 9/1,093 malignancies, risk 0.8%), high risk (predictive model value ≥2.3%: 43/566 malignancies, risk 7.6%). ConclusionThe preoperative three-class diagnostic algorithm and risk class system can stratify women according to risk of malignancy. Our findings, if confirmed in a multicentre study, will permit differentiation between benign and MUMs allowing a personalized clinical approach. FundingNothing to declare.

Implicating clinical utility of altered expression of PTCH1 & SMO in oral squamous cell carcinoma.

Oral cancer poses a significant burden on public health in India, with higher incidence and mortality rates. Despite advancements in treatment modalities, prognosis remains poor due to factors such as localized recurrence and lymph node metastasis, potentially influenced by cancer stem cells. Among signaling pathways implicated in CSC regulation, the Hedgehog pathway plays a crucial role in oral squamous cell carcinoma (OSCC). 97 OSCC patients' tissue samples were collected and subjected to RNA isolation, cDNA synthesis and quantitative real-time PCR to analyze PTCH1 and SMO expression. Protein expression was assessed through immunohistochemistry. Clinicopathological parameters were correlated with gene and protein expression. Statistical analysis included Pearson chi-square tests, co-relation co-efficient tests, Kaplan-Meier survival analysis and ROC curve analysis. PTCH1 expression correlated with lymphatic permeation (p = 0.002) and tumor stage (p = 0.002), while SMO expression correlated with lymph node status (p = 0.034) and tumor stage (p = 0.021). PTCH1 gene expression correlated with lymph node status (p = 0.024). High PTCH1 gene expression was associated with shorter survival in tongue cancer patients. ROC curve analysis indicated diagnostic potential for PTCH1 and SMO gene and cytoplasmic SMO expression in distinguishing malignant tissues from adjacent normal tissues. PTCH1 and SMO play a crucial role in oral cancer progression, correlating with tumor stages and metastatic potential. Despite not directly influencing overall survival, PTCH1 expression at specific anatomical sites hints at its prognostic implications. PTCH1 and SMO exhibit diagnostic potential, suggesting their utility as molecular markers in oral cancer management and therapeutic strategies.