Endometrial cancer (EC) is a malignancy of the endometrial epithelium. The prevalence and mortality rates associated with the disease are on the rise globally. A total of 20 cases of type I EC tissues were collected for transcriptomic sequencing, our findings indicate that PAX2 is highly expressed in EC tissues and is closely related to the pathogenesis of EC. PAX2 is a member of the paired homeobox domain family and has been linked to the development of a number of different tumours. In normal endometrial tissue, PAX2 is methylated; however, in EC, it is demethylated. Nevertheless, few studies have focused on its role in EC. A protein-protein interaction (PPI) analysis revealed a regulatory relationship between PAX2 and CD133, which in turn affects the activity of AKT1. CD133 is a well-known marker of tumor stem cells and is involved in tumor initiation, metastasis, recurrence, and drug resistance; AKT1 promotes cell survival by inhibiting apoptosis and is considered a major promoter of many types of cancer. Nevertheless, further investigation is required to ascertain whether PAX2 affects the progression of EC by regulating the CD133-AKT1 pathway. The present study demonstrated that PAX2 promoted cell proliferation, migration, invasion and adhesion, and inhibited apoptosis. Its mechanism of action was found to be the inhibition of mitochondrial oxidative phosphorylation, promotion of glycolysis, increase in mitochondrial copy number, and increase in the levels of reactive oxygen species (ROS) and hexokinase, as well as the concentration of mitochondrial calcium ions. This was achieved through the promotion of CD133 expression and the phosphorylation of AKT1. In conjunction with the aforementioned regulatory pathways, the progression of EC is facilitated.

Lung carcinoma is the leading cause of mortality globally, posing a significant public health concern. Fluorescent-mediated tumor imaging is emerging as a novel diagnostic and therapeutic approach in clinical practice. Nevertheless, traditional probes lack accuracy in diagnosing tumors due to the overlap in baseline values of certain tumor biomarkers between normal and tumor cells as both exhibit turn-on fluorescence, rendering it impossible to distinguish tumor tissue from normal tissue with high resolution. We introduce a sensing strategy that constructs a probe with an elevated biomarker response-threshold and targeting ability for the endoplasmic reticulum (ER), enabling precise distinction between tumor and normal cells, and successfully develop such a probe. Elevating the response-threshold is advantageous in minimizing interference from baseline values of biomarkers in normal cells. Additionally, targeting the ER ensures that the probe's response range is consistent with the biomarker content in the ER, collectively enhancing differentiation between normal and cancer cells. Using this novel probe, a distinct bright fluorescence signal from tumors could be observed in confocal imaging of tumor tissues from tumor-bearing mice after intravenous injection, in stark contrast to the limited fluorescence emanating from normal tissues. Furthermore, this probe demonstrated exceptional precision in distinguishing clinical lung cancer tissue from para-cancer tissue. This work presents a more reliable tumor detection strategy, capable of accurate diagnosis even when the biomarker is highly expressed in both normal and tumor tissues. It promises to be a valuable tool for future clinical applications, particularly in intraoperative assisted resection.

(1) Background: The management of ipsilateral breast cancer recurrence depends on the extent of the tumor, and staging results, and mastectomy is currently the standard of care for previously irradiated patients. Studies are increasingly investigating suitable candidates for the repeated use of breast-conserving approaches as an alternative to mastectomy. But this includes the crucial necessity for curative reirradiation (Re-RT). The therapeutic challenge in reirradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy, intraoperative radiotherapy, or external beam RT with photons or electrons. The application of particle therapy using proton beam therapy represents an innovative radiotherapeutic technique for breast cancer patients that might offer advantageous physical properties, a superior dose reduction to adjacent organs-at-risk, and effective target volume coverage with lower integral doses to the patient's whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses. (2) Methods: The BREAST trial (NCT06954623) will be conducted as a prospective, single-arm, phase II study in 20 patients with histologically proven invasive breast cancer recurrences after repeat breast-conserving surgery and with an indication for local reirradiation. The patients will receive partial-breast re-RT with proton beam therapy in 15 once-daily fractions up to a total dose of 40.05 Gy(RBE), delivered with active raster scanning. The required time interval will be 1 year after previous RT to the ipsilateral breast. (3) Results: The following results will be reported: The primary endpoint is defined as the cumulative overall occurrence of (sub)acute skin toxicity of grade ≥ 3 within 6 months after the start of re-RT. Secondary outcome includes an analysis of the local, regional, and distant control, progression-free and overall survival, quality of life, and cosmesis. The explorative and translational objectives of this study include planning comparisons to other RT techniques and irradiation types, dosimetric evaluations, analyses of radiological imaging features, and translational assessments of cardiac toxicity biomarkers and tumor markers. (4) Conclusions: Overall, the aim of this study is to evaluate the potential of proton beam therapy for partial breast reirradiation and to establish the underlying data for a randomized trial.

The aim of this research was to examine the feasibility and effects of the "Rebuilding Myself" intervention to enhance adaptability of cancer patients to return to work.

A randomized controlled trial with a two-arm, single-blind design was employed. The control group received usual care, whereas the intervention group received "Rebuilding Myself" interventions. The effects were evaluated before the intervention, mid-intervention, and post-intervention. The outcomes were the adaptability to return to work, self-efficacy of returning to work, mental resilience, quality of life, and work ability.

The results showed a recruitment rate of 73.17%, a retention rate of 80%. Statistically significant differences were found between the two groups in cancer patients' adaptability to return to work, self-efficacy to return to work, mental resilience, and the dimension of bodily function, emotional function, fatigue, insomnia, and general health of quality of life.

"Rebuilding Myself" intervention was proven to be feasible and can initially improve cancer patients' adaptability to return to work. The intervention will help provide a new direction for clinicians and cancer patients to return to work.

Squamous differentiation in prostate cancer is rare, presenting unique diagnostic and therapeutic challenges. We report a case of high-grade prostatic adenocarcinoma with focal squamous differentiation in a 73-year-old man without prior radiation or androgen deprivation. Immunohistochemistry confirmed the squamous component arose from the adenocarcinoma, not a separate malignancy. This case highlights the importance of morphological assessment and strategic immunohistochemical evaluation to distinguish prostate cancer variants. A biopsy capturing only the squamous component could have led to misdiagnosis and inappropriate treatment. To improve diagnostic accuracy and management, we propose the term 'adenocarcinoma with focal squamous differentiation' over adenosquamous carcinoma.

The present study aimed to investigate the role of 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 4 (PFKFB4) in endometrial cancer cells and to explore its potential molecular mechanisms. PFKFB4 expression in endometrial cancer tissues was detected by immunohistochemistry. Cell Counting Kit‑8, Transwell assays and flow cytometry were used to detect cell proliferation, invasion and apoptosis in endometrial cancer cells after PFKFB4 knockdown. An enzyme‑linked immunosorbent assay was used to detect the glucose and lactic acid contents. Western blotting was performed to detect the levels of glycolysis‑related enzymes, steroid receptor coactivator‑3 (SRC‑3), and phosphorylated SRC‑3. In vivo experiments were performed to investigate the tumorigenic potential of PFKFB4. PFKFB4 expression was upregulated in endometrial cancer tissues compared with that in normal controls, and its upregulation was positively correlated with the depth of myometrial invasion, lymph node metastasis, surgical pathological stage and vascular invasion. PFKFB4 knockdown significantly inhibited proliferation and invasion, increased apoptosis, and decreased oxygen consumption and lactic acid production in endometrial cancer cells. PFKFB4 knockdown decreased SRC‑3 phosphorylation. After simultaneous PFKFB4 knockdown and SRC‑3 overexpression in cancer cells, oxygen consumption, lactic acid production, and glycolysis‑related protein expression were increased compared with those in control cells. PFKFB4 knockdown inhibited tumor proliferation, apoptosis and the expression of Ki‑67. PFKFB4 may regulate glycolysis in endometrial cancer cells by targeting SRC‑3, thus promoting endometrial cancer progression.

Cancer (malignant tumor), a serious disease with a high mortality rate, early-stage diagnosis and treatment are very important for cancer therapy. The average concentration of reactive oxygen species (ROS) in cancer cells is ten times higher than in normal cells, and the overexpression of hypochlorous acid (HClO) is closely associated with cancer progression. Herein, a novel near-infrared (NIR) Golgi apparatus-targetable (GA) fluorescent probe GA-BOD-S was synthesized using the BODIPY and phenothiazine as the basic fluorescence framework for HClO monitoring. GA-BOD-S exhibited a colorimetric and ratiometric dual-mode recognition for HClO with the excellent merits including low detection limit (35 nM), fast response time (within 13 s), and exceptional GA targeting capability (Pearson's coefficient 0.98). Notably, both fluorescence emission wavelengths of GA-BOD-S before and after reaction with HClO are located in the NIR region, significantly enhancing the quality of fluorescence imaging in vivo. Cellular experiments revealed that GA-BOD-S can effectively visualize both endogenous and exogenous HClO within cells and living zebrafish. GA-BOD-S was successfully employed for high-contrast imaging of cancer cells and normal cells based on the differences in intracellular ROS levels, and achieved in-situ imaging of tumors in vivo. Furthermore, the precision of tumor resection surgery was significantly improved under the guidance of fluorescence probe GA-BOD-S, which provided a new perspective for the diagnosis and treatment of cancer disease.

Endometrial cancer (EC), a prevalent and intricate disease, is associated with a poor prognosis among gynecological malignancies. Its incidence rising globally underscores the urgent need for biomarkers detection in both research and clinical settings. Over the past decade, we've witnessed rapid advancements in biological methodologies and techniques. A multitude of omics technologies, encompassing genomic/transcriptomic sequencing and proteomic/metabolomic mass spectrometry, have been extensively employed to analyze both tissue and liquid samples derived from EC patients. The integration of multi-omics data has not only broadened our understanding of the disease but also unearthed valuable biomarkers specific to EC. This review encapsulates the recent progress and future prospects in the application of multi-omics technologies in EC research, emphasizing the potential of multi-omics in uncovering novel biomarkers and enhancing clinical assessments.

Integration of palliative and supportive care in cancer treatment pathways is becoming standardised. While there has been significant qualitative research in oncology on palliative and supportive care integration into clinical care, there is little evidence that focusses on clinicians who manage hepatocellular carcinoma (HCC) and their perceptions on palliative and supportive care.

To investigate the attitudes and perceptions regarding palliative and supportive care of healthcare professionals managing patients with HCC.

Qualitative study involving semi-structured individual interviews transcribed verbatim and analysed thematically.

A total of 25 healthcare professionals including hepatologists, gastroenterology trainees, hepatology clinical nurse consultants, social workers, and palliative care specialists providing care to patients with HCC recruited at 4 tertiary hospitals via purposive sampling.

The following themes emerged: (1) availability of palliative care services, (2) need for clear referral pathways and processes, (3) patients' limited understanding of palliative care, (4) recognition of benefits of palliative care, and (5) the lack of training in hepatology services for palliative care provision.

Health professionals' perceptions of integration of palliative and supportive care in liver cancer care are hampered by multiple barriers. Opportunities to establish a more cohesive approach to care integration for patients with liver cancer have been identified.  TRIAL REGISTRATION: ACTRN12623000010695 (date of registration 9/01/2023).   What is already known about the topic? • Integration of palliative and supportive care for cancer can have profound benefits for patients' symptom burden and quality of life. • There is a lack of empirical studies examining the perspectives of health professionals who manage liver cancer on the integration of palliative and supportive care into the treatment pathways for patients. What this paper adds • This study identifies a number of barriers to the implementation of palliative and supportive care into liver cancer treatment algorithms. • The absence of sufficient evidence in clinical guidelines impairs the capacity of health professionals to improve the integration of palliative and supportive care for liver cancer patients. Implications for practice, theory, or policy. • As liver cancer prevalence increases, further effort is required to develop appropriate evidence-based clinical guidelines and referral pathways to support the integration of palliative and supportive care within existing liver cancer services.

Endometrial cancer (EC) is one of the most common cancers in women, with a short overall survival and poor prognosis. Besides the biologically aggressive EC properties, Cancer-associated cachexia is the main factor. However, the detailed mechanism underlying EC-related cachexia and its harmful effects on EC progression and patient prognosis remains unclear.

For clinical specimen and the vitro experiment, we detected TRIM22 expression level, EC patients' survival time, EC cell functional change, and adipose thermogenic changes to identify the function of TRIM22 in EC progression, EC-associated cachexia, and their molecular mechanisms. Then, for the vivo experiment, we exploited the xenografts in mice to identify the function of TRIM22 again, and to screen the drug therapeutic schedule.

Herein, we demonstrated that TRIM22 inhibited EC cell growth, invasion, and migration. Interleukin (IL)-6 mediated brown adipose tissue activation and white adipose tissue browning which induced EC-related cachexia. TRIM22 suppressed the EC cells' secretion of IL-6, and IL-6 mediated EC-related cachexia. Mechanistically, TRIM22 inhibited EC progression by suppressing the nucleotide-binding oligomerization domain 2(NOD2)/nuclear factor-kappaB (NF-κB) signaling pathway, with the purpose of impeding the production of IL-6. Moreover, we revealed that TRIM22 inhibited EC-associated cachexia by suppressing the IL-6/IL-6 receptor (IL-6R) signaling pathway. Therapeutically, we demonstrated that combination treatment with a TRIM22 inducer (progesterone) and a thermogenic inhibitor (IL-6R antibody) synergistically augmented the antitumor efficacy of carbotaxol (carboplatin and paclitaxel), in vivo.

Our data reveals that TRIM22-EC-IL-6-cachexia cross-communication has important clinical relevance and that the use of combined therapy holds great promise for enhancing the efficacy of anti-ECs. (Fig. graphical abstract).

Endometrial cancer (EC) is increasing incidence among women, and it constitutes a health problem for women globally. An important aspect of EC management involves the use of protein biomarkers for early detection and monitoring. Protein biomarkers allow the identification of high-risk patients, the detection of the disease in its early stages, and the assessment of treatment responses. Mass spectrometry (MS)-based proteomics offers robust analytical techniques and a comprehensive understanding of proteins. Proteomics methods allow scientists to investigate both the quantities and functions of proteins. Thus, it provides valuable insights into how proteins are altered under different conditions. This review summarizes recent advances in MS-based proteomic biomarker discovery for EC, focusing on different sample types and MS-based techniques used in clinical studies. The review emphasized in detail the most commonly used key sources such as blood, urine, vaginal fluids and tissue. Furthermore, MS-based proteomics techniques such as untargeted, targeted, sequential window acquisition of all theoretical mass spectra (SWATH-MS) and mass spectrometry imaging used in the discovery and validation/validation phases were evaluated. This review highlights the importance of biomarker discovery and clinical translation to improve diagnostic and therapeutic outcomes in EC. It aims to provide a comprehensive overview of MS-based proteomics in EC, guiding future research and clinical applications.

To evaluate the efficacy and safety of docetaxel/cisplatin chemotherapy followed by pelvic radiation therapy after staging surgery in patients with high-risk endometrial cancer.

In this open-label, single-arm, phase 2 trial conducted at 2 South Korean centers, we enrolled patients with histologically confirmed endometrial cancer who had undergone staging surgery. Inclusion criteria were based on International Federation of Gynecology and Obstetrics (FIGO) Staging 2009: stage I patients with ≥2 risk factors (grade 3, positive lymphovascular invasion, more than half of myometrium invasion); stage IB and II patients with clear cell or serous adenocarcinoma; stage II patients post-type 1 hysterectomy; and patients at stage III. Patients underwent 3 cycles of chemotherapy with docetaxel (70 mg/m2) and cisplatin (60 mg/m2) followed by pelvic radiation therapy ranging from 45 to 50.4 Gy. Disease status and adverse events were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events 4.0, respectively, with scheduled imaging and assessments throughout the study.

A total of 62 patients were included in this study and were followed for a median duration of 65 months (IQR, 48-86 months). The progression-free survival rates at 1, 3, and 5 years were 98.4%, 86.9%, and 79.1%, respectively. The overall survival rates at 1, 3, and 5 years were 98.4%, 96.4%, and 96.4%, respectively. After chemotherapy, 62.9% of patients experienced severe neutropenia, with 3.2% having grade 3 or 4 anemia. Common mild side effects included nausea (58.1%) and alopecia (38.7%). Postradiation, 16.7% experienced grade 3 neutropenia, and a few had grade 1 or 2 anemia (3.3%), with most other side effects being mild and no critical toxicities reported.

Patients with endometrial cancer with high-risk factors could benefit from adjuvant chemotherapy using docetaxel/cisplatin, followed by radiation therapy, with manageable toxicities.

The microcystic, elongated, and fragmented (MELF) pattern, characterized by myxoid and inflamed stroma, is readily identifiable as a form of myometrial infiltration. This meta-analysis endeavors to assess the prognostic significance of MELF infiltration patterns in patients diagnosed with endometrial cancer.

A comprehensive literature search, spanning until 11 October 2023, across PubMed , Embase , Cochrane , and Web of Science databases, identified 23 relevant studies involving 5199 patients. Data analysis was performed using Stata 16.0.

Analysis indicates that MELF infiltration predicts a higher risk of lymph node metastasis in endometrial cancer patients [hazard ratios (HR) = 5.05; 95% confidence interval (CI), 3.62-7.05; P  < 0.05]. Notably, this association remains consistent across various patient demographics, analytical approaches, study designs, and treatment modalities. However, MELF infiltration does not significantly correlate with recurrence (HR = 1.05; 95% CI, 0.73-1.52; P  > 0.05), overall survival (HR = 1.24; 95% CI, 0.91-1.68; P  > 0.05), or disease-free survival (HR = 1.40; 95% CI, 0.85-2.28; P  > 0.05).

While MELF infiltration heightens the risk of lymph node metastasis in endometrial cancer, its impact on recurrence, overall survival, and disease-free survival remains statistically insignificant.

Background: We are experiencing an increasing number of patients presenting with advanced malignancy who are also presenting with chronic limb threatening ischemia. Method: With advancements in medicine and surgery, we are suggesting a shift in mindset of how we treat this group of patients and proposing a more holistic approach for treatment options. Result: In this original article, we highlight our approach in managing such patients and suggest an algorithm. Conclusions: We hope that our article brings awareness and assists vascular surgeons in managing such cases, resulting in improved quality of life for these patients.

The occurrence and progression of cancer is a significant focus of research worldwide, often accompanied by a prolonged disease course. Concurrently, researchers have identified that social determinants of health (SDOH) (employment status, family income and poverty ratio, food security, education level, access to healthcare services, health insurance, housing conditions, and marital status) are associated with the progression of many chronic diseases. However, there is a paucity of research examining the influence of SDOH on cancer incidence risk and the survival of cancer survivors. The aim of this study was to utilize SDOH as a primary predictive factor, integrated with machine learning models, to forecast both cancer risk and prognostic survival. This research is grounded in the SDOH data derived from the National Health and Nutrition Examination Survey dataset spanning 1999 to 2018. It employs methodologies including adaptive boosting, gradient boosting machine (GradientBoosting), random forest (RF), extreme gradient boosting, light gradient boosting machine, support vector machine, and logistic regression to develop models for predicting cancer risk and prognostic survival. The hyperparameters of these models-specifically, the number of estimators (100-200), maximum tree depth (10), learning rate (0.01-0.2), and regularization parameters-were optimized through grid search and cross-validation, followed by performance evaluation. Shapley Additive exPlanations plots were generated to visualize the influence of each feature. RF was the best model for predicting cancer risk (area under the curve: 0.92, accuracy: 0.84). Age, non-Hispanic White, sex, and housing status were the 4 most important characteristics of the RF model. Age, gender, employment status, and household income/poverty ratio were the 4 most important features in the gradient boosting machine model. The predictive models developed in this study exhibited strong performance in estimating cancer incidence risk and survival time, identifying several factors that significantly influence both cancer incidence risk and survival, thereby providing new evidence for cancer management. Despite the promising findings, this study acknowledges certain limitations, including the omission of risk factors in the cancer survivor survival model and potential biases inherent in the National Health and Nutrition Examination Survey dataset. Future research is warranted to further validate the model using external datasets.

Individuals with lung cancer are living longer due to recent treatment advances such as immunotherapy and targeted therapy. The preferred label(s) of this new population are unknown. This is important as personal/advocacy benefits have been reported by using "survivor" or "thriver" by some groups; however, these same labels have been rejected by others. The goal of the present study was to explore the meaning of different labels and reasons given for preferred label(s) among people diagnosed with advanced lung cancer receiving these treatments.

The study is part of a larger project conducted in partnership with Lung Cancer Canada to identify the supportive care needs of individuals with advanced lung cancer receiving immunotherapy or targeted therapy. Participants (n = 24) were recruited across Canada. In-depth qualitative interviews were coded using reflexive thematic analysis.

Labels are important and serve four functions: meaning-making, acceptance, maintaining a positive outlook, and shaping how people in participants' circle understand and react to them. Participants felt their experience did not fit traditional labels. While "survivor" was associated with maintaining a positive outlook by some, it was strongly rejected by others as it implied a cure. Some felt "patient" conveyed realism, but others found it deprived them of empowerment. "Person living with cancer" was perceived as reflecting the ongoing nature of the disease while not overly centring cancer within a person's identity.

Participants identified with various labels and emphasized how the label reflected their identity and psychological experiences of the disease. Thus, it is important that clinicians elicit and use individuals' preferred terms, and default to person-first language if unknown.

Lactamase β (LACTB) inhibits the metastasis and progression of multiple malignant tumors. However, little is known about its role in endometrial cancer (EC). Our study aimed to investigate the function and potential molecular mechanism of LACTB in modulating EC progression.

LACTB expression was measured via immunohistochemistry staining, Western blot and qRT-PCR. The role of LACTB in EC was investigated both in vivo and in vitro by employing xenograft mice models and using colony formation, EdU, and Transwell assays, along with flow cytometric analysis. In addition, to assess LACTB function on lipid metabolism, lipid droplets in EC cells were labeled with Nile red. Western blot, immunofluorescence staining, co-immunoprecipitation, ubiquitination assay, and cycloheximide chase assay and rescue experiments were performed to confirm the interaction between LACTB, p53, and MDM2 in EC.

LACTB expression was downregulated in EC. LACTB inhibited the malignant phenotypes and reprogramed lipid metabolism in EC cells. Moreover, LACTB significantly upregulated p53 by attenuating the MDM2-mediated ubiquitination and degradation of p53. Besides, LACTB silencing facilitated the malignant phenotypes and reprogramed lipid metabolism in EC cells; this was reversed with p53 overexpression. LACTB knockdown facilitated EC progression via downregulating p53 in vivo.

LACTB repressed EC cell proliferation and metastasis, and reprogramed lipid metabolism via attenuating the MDM2-mediated ubiquitination and degradation of p53.

The Cancer Genome Atlas identified four distinct molecular subtypes of endometrial cancer (EC): POLE mutated, mismatch repair deficient (dMMR), copy number low, and copy number high. The goal of this review is to summarize the profound clinical implications of molecular subtyping, particularly in guiding treatment decisions for dMMR and microsatellite instability high (MSI-H) EC.

Clinical trials have demonstrated the remarkable efficacy of immunotherapy in dMMR/MSI-H EC tumors. Trials including GARNET, KEYNOTE-158, NRG GY-018, and RUBY have shown significant improvements in clinical outcomes for patients with advanced and recurrent disease, leading to FDA approvals for immunotherapy in both frontline and recurrent EC treatment settings.Building on these successes, recent studies, including DUO-E, are exploring combination therapies to enhance the efficacy of immunotherapy in EC. Simultaneously, trials including NRG GY-020, are investigating the potential benefits of immunotherapy in early-stage disease.

Immunotherapy therapy has revolutionized the treatment of endometrial cancer in both upfront and recurrent settings, with molecular subtyping identifying patients most likely to benefit, especially those with dMMR/MSI-H tumors.

Endometrial Carcinoma (UCEC) is a prevalent malignant tumor within the female reproductive system. HLA-DMB, the beta chain of the non-classical MHC class II protein HLA-DM, has been implicated in the progression of various cancers. However, its role in the development of endometrial carcinoma remains unclear. Therefore, we conducted a preliminary exploration of the prognostic value and potential mechanisms of HLA-DMB in uterine corpus endometrial carcinoma (UCEC).

The differential expression of HLA-DMB was analyzed in 554 tumor samples and 35 normal samples obtained from the TCGA database. The differential expression of HLA-DMB across various cancers, along with immune infiltration analysis, was conducted using the TIMER2.0 database. Additionally, the expression of HLA-DMB in endometrial carcinoma was examined in the GEPIA2 database, along with its relationship to prognosis. Furthermore, TISIDB was utilized to predict the relationships between HLA-DMB and various immune enhancement factors as well as immunosuppressive factors. Gene Ontology (GO) analysis and Gene Set Enrichment Analysis (GSEA) were employed to explore the signaling pathways associated with HLA-DMB in endometrial cancer. Univariate COX regression analysis was performed to identify prognostic factors for endometrial carcinoma (EC), and a multivariate COX proportional hazards regression model was used to confirm that HLA-DMB can serve as an independent prognostic factor for EC. The protein interaction network of HLA-DMB was constructed using the STRING database, and the chemical drugs related to HLA-DMB were predicted through the CTD database. Finally, the expression of HLA-DMB was validated by qPCR and immunohistochemistry.

The expression of HLA-DMB at both mRNA and protein levels is significantly higher in UCEC tissues compared to normal tissues. Prognostic analyses indicate that increased expression of HLA-DMB correlates with improved patient prognosis, suggesting its potential as an independent prognostic factor for UCEC. Furthermore, in endometrial cancer, elevated levels of HLA-DMB are associated with higher immune infiltration scores and are closely related to various immune-enhancing factors. Mechanistically, HLA-DMB primarily participates in CD22-mediated regulation of B cell receptors (BCR), leading to BCR antigen activation and the production of second messengers. In our drug analysis, we identified several chemical agents associated with HLA-DMB, including cisplatin, dexamethasone, and ethinylestradiol.

This study elucidates the function and underlying mechanisms of HLA-DMB in UCEC, providing a potential biomarker and target for immunotherapy in this disease.

Lung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of cases. Due to the lack of early clinical signs, metastasis often occurs before diagnosis, impacting treatment and prognosis. Cardiovascular disease (CVD) is a common comorbidity in lung cancer patients, with shared risk factors exacerbating outcomes.

This study investigates the association between coronary artery calcium (CAC) scores, major adverse cardiovascular events (MACE), and survival outcomes in NSCLC patients, utilizing positron emission tomography-computed tomography (PET-CT) for CAC scoring. A retrospective cohort study of 154 NSCLC patients (mean age 66.3 years, 52% women) at the University of Utah (2005-2022) was conducted. Baseline PET-CT or CT imaging was used to quantify CAC scores, categorized into five risk levels. Cox proportional hazards and logistic regression analyses assessed the impact of CAC scores on survival and cardiovascular events, adjusting for confounders such as age, gender, and smoking status.

Higher CAC scores were significantly associated with increased MACE, acute myocardial infarction (MI), and poorer overall survival. The severe risk CAC score group had significantly lower survival (p = 0.022). Logistic regression revealed a strong association between higher CAC scores and MI incidence (moderate: OR = 13.8, severe: OR = 21.2) and MACE (severe: OR = 10.2). Smoking history was a significant predictor of overall survival (p = 0.006).

CAC scoring via PET-CT provides valuable prognostic insights in NSCLC patients, highlighting the need for integrated cardiovascular risk management in this population. Further research and advanced technologies like machine learning could enhance CAC scoring application in clinical practice.

Retrospectively registered.

Group health coaching (GHC) may be a suitable method for supporting healthy lifestyle behaviors in cancer patients and survivors. The aim of this scoping review was to explore GHC interventions targeting this population, specifically examining program composition and measured outcomes. A systematic search strategy was used to identify intervention studies focused on GHC with cancer patients and survivors. Seven studies met the criteria. Studies focused on physical activity, diet, weight loss, or some combination thereof utilizing GHC by itself or as one component of an exercise and/or diet intervention. There was a wide range of measured outcomes, grouped into: feasibility/acceptability; physical activity/exercise; body composition and biomarkers; diet; distress, quality of life, fatigue; and other. Overall, studies were found to be feasible and showed positive results for weight loss, diet, and quality of life. Findings for changes in physical activity, distress, and fatigue were mixed. Additionally, variability was found in many of the GHC components. This review suggests GHC for cancer patients and survivors is still in the nascent stages. However, these studies were deemed feasible and satisfactory to participants, with positive outcomes noted. While still in the early stages, GHC appears promising for supporting positive lifestyle behaviors in this population.

Cell division cycle 6 (CDC6) is essential for the initiation of DNA replication in eukaryotic cells and contributes to the development of various human tumors. Polycystic ovarian syndrome (PCOS) is a reproductive endocrine disease in women of childbearing age, with a significant risk of endometrial cancer (EC). However, the role of CDC6 in the progression of PCOS to EC is unclear. Therefore, we examined CDC6 expression in patients with PCOS and EC. We evaluated the relationship between CDC6 expression and its prognostic value, potential biological functions, and immune infiltrates in patients with EC. In vitro analyses were performed to investigate the effects of CDC6 knockdown on EC proliferation, migration, invasion, and apoptosis. CDC6 expression was significantly upregulated in patients with PCOS and EC. Moreover, this protein caused EC by promoting the aberrant infiltration of macrophages into the immune microenvironment in patients with PCOS. A functional enrichment analysis revealed that CDC6 exerted its pro-cancer and pro-immune cell infiltration functions via the PI3K-AKT pathway. Moreover, it promoted EC proliferation, migration, and invasion but inhibited apoptosis. This protein significantly reduced EC survival when mutated. These findings demonstrate that CDC6 regulates the progression of PCOS to EC and promotes immune infiltration.

Background/Objectives: This study investigates which demographic, clinical and pathological factors of women with early-stage presurgical EC could be considered risk factors for the presence of different subtypes of metastases in sentinel lymph nodes (SLNs). Methods: This is a retrospective single-center study that collected data between December 2015 and April 2024. EC patients who underwent total hysterectomy with salpingo-oophorectomy and SLN mapping with indocyanine green (ICG) were recorded. Results: Data from 98 women with EC were analyzed. The endometrioid histotype was present in 85 (86%) women, and the non-endometrioid histotype was present in 13 (13%) women. High-grade EC (G3) was present in 21 (21.4%) patients, and low-grade EC (G1-G2) was present in 77 (78.6%) patients. The total number of women with SLN metastasis was 21/98 (21%). Of 21 women, 5 had MAC, 6 had MIC and 10 had ITCs. Conclusions: Preliminary analysis identified three risk factors for nodal involvement: age greater than 67 years, high-grade endometrial carcinomas and myometrial invasion greater than or equal to 50%. Lymphovascular space invasion, histotype 2 and p53 mutation showed a slight, but not statistically significant, tendency to be risk factors for SLN positivity. A deeper analysis with univariate uninominal logistic regression showed that high-grade EC is related to a greater probability of MACs, as shown in other studies, and that low-grade EC (grades 1 and 2) had a strong relationship with low-volume metastasis (LVM); further studies are needed to confirm these results.

Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5, 4b, and 4a possessed potent cytotoxic activity against PC-3 cells with IC50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC50 8.5 µM. Moreover, compound 5 exhibited potent inhibitory activity on EFGR with IC50 0.1812 µM, as well as PI3Kβ inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kβ inhibiting activity. Docking aligns with the in vitro results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound 5 decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound 5 caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways.

We consider evaluating biomarkers for treatment selection under assay modification. Survival outcome, treatment, and Affymetrix gene expression data were attained from cancer patients. Consider migrating a gene expression biomarker to the Illumina platform. A recent novel approach allows a quick evaluation of the migrated biomarker with only a reproducibility study needed to compare the two platforms, achieved by treating the original biomarker as an error-contaminated observation of the migrated biomarker. However, its assumptions of a classical measurement error model and a linear predictor for the outcome may not hold. Ignoring such model deviations may lead to sub-optimal treatment selection or failure to identify effective biomarkers. To overcome such limitations, we adopt a nonparametric logistic regression to model the relationship between the event rate and the biomarker, and the deduced marker-based treatment selection is optimal. We further assume a nonparametric relationship between the migrated and original biomarkers and show that the error-contaminated biomarker leads to sub-optimal treatment selection compared to the error-free biomarker. We obtain the estimation via B-spline approximation. The approach is assessed by simulation studies and demonstrated through application to lung cancer data.

Endometrial cancer is one of the most common gynecological malignancies, and while early-stage cases are highly treatable, recurrent or advanced EC remains challenging to manage. Immunotherapy, particularly immune checkpoint inhibitors, has revolutionized treatment approaches in oncology, and its application in EC has shown promising results. Key to immunotherapy efficacy in EC is the tumor's mismatch repair status, with MMR-deficient tumors demonstrating a higher tumor mutational burden and increased PD-L1 expression, making them more susceptible to immune checkpoint inhibitors (ICIs) such as pembrolizumab, durvalumab, and dostarlimab. However, not all mismatch repair-deficient (MMRd) tumors respond to ICIs, particularly those with a "cold" tumor microenvironment (TME) characterized by poor immune infiltration. In contrast, some MMR-proficient tumors with a "hot" TME respond well to ICIs, underscoring the complex interplay between MMR status, tumor mutational burden (TMB), and TME. To overcome resistance in cold tumors, novel therapies, including Chimeric Antigen Receptor (CAR) T cells and tumor-infiltrating lymphocytes are being explored, offering targeted immune-based strategies to enhance treatment efficacy. This review discusses the current understanding of immunotherapy in EC, emphasizing the prognostic and therapeutic implications of MMR status, TME composition, and emerging cell-based therapies.

There is a significant association between cardiovascular diseases (CVD) and prostate cancer (PCa), leading to high mortality. This study evaluates the trends in mortality associated with CVDs and PCa among older (≥ 65 years) men in the United States (US).

This analysis utilized the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). The analysis of Multiple Cause of Death Files was carried out from 1999 to 2019 to identify fatalities with CVD and PCa listed as either contributory or underlying causes of death. Crude and age-adjusted mortality rates (AAMRs) per 100,000 populations for variables such as year, race and ethnicity, and geographic regions were determined. To assess annual percent change (APC), a Joinpoint regression program was employed.

Overall AAMR was 54.3 in 1999 and 34.6 in 2019. After a decline in AAMR from 1999 to 2015, an alarming rise in mortality was observed until 2019. Mortality rates were highest among Non-Hispanic (NH) Black and African American men (74.9). Geographically, the highest mortalities were witnessed in the West (46.4) and non-metropolitan areas (44.6). States with AAMRs ranking in the 90th percentile were Nebraska, California, North Dakota, the District of Columbia, and Mississippi.

After decreasing death rates associated with CVD and PCa from 1999 to 2015, a reversal in the trend was observed from 2015 to 2019. Addressing this increase in death rates, especially among the vulnerable population, requires focused attention and targeted strategies to implement necessary safeguards in the upcoming years.

Prostate cancer (PCa) is the most diagnosed noncutaneous malignancy and second leading-cause of cancer death in men, yet screening is decreasing. As PCa screening has become controversial, socioeconomic disparities in PCa diagnosis and outcomes widen. This study was designed to determine the current disparities influencing PCa diagnosis in Charlotte, NC.

The Levine Cancer Institute database was queried for patients with PCa, living in metropolitan Charlotte. Socioeconomic status (SES) was determined by the Area Deprivation Index (ADI); higher ADI indicated lower SES. Patients were compared by their National Comprehensive Cancer Network risk stratification. Artificial intelligence predictive models were trained and heatmaps were created, demonstrating the geographic and socioeconomic disparities in late-stage PCa.

Of the 802 patients assessed, 202 (25.2%) with high-risk PCa at diagnosis were compared with 198 (24.7%) with low-risk PCa. High-risk PCa patients were older (69.8 ± 9.0 vs. 64.0 ± 7.9 years; p < 0.001) with lower SES (ADI block: 98.4 ± 20.9 vs. 92.1 ± 19.8; p = 0.004) and more commonly African-American (White: 66.2% vs. 78.3%, African-American: 31.3% vs. 20.7%; p = 0.009). On regression, ADI block was an independent predictor (odds ratio [OR] = 1.013, 95% confidence interval [CI] 1.002-1.024; p = 0.024) of high-risk PCa at diagnosis, whereas race was not (OR = 1.312, 95% CI 0.782-2.201; p = 0.848). A separate regression demonstrated higher ADI (OR = 1.016, 95% CI 1.004-1.027; p = 0.006) and older age (OR = 1.083, 95% CI 1.054-1.114; p < 0.001) were independent predictors for high-risk PCa. Findings, depicted in heatmaps, demonstrated the geographic locations where men with PCa were predicted to have high-risk disease based on their age and SES.

Socioeconomic status was more closely associated with high-risk PCa at diagnosis than race. Although, of any variable, age was most predictive. The heatmaps identified areas that would benefit from increased awareness, education, and screening to facilitate an earlier PCa diagnosis.

Tumor-associated macrophages (TAMs), as key components of tumor microenvironment (TME), exhibit phenotypic plasticity in response to environmental cues, causing polarization into either pro-inflammatory M1 phenotypes or immunosuppressive M2 phenotypes. Although TAM has been widely studied for its crucial involvement in the initiation, progression, metastasis, and immune regulation of cancer cells, there have been limited attempts to understand how the metastatic potentials of cancer cells influence TAM polarization within TME. Here, we developed a miniaturized TME model using a 3D hybrid system composed of murine melanoma cells and macrophages, aiming to investigate interactions between cancer cells exhibiting various metastatic potentials and macrophages within TME. The increase in spheroid size within this model was associated with a reduction in cancer cell viability. Examining macrophage surface marker expression and cytokine secretion indicated the development of diverse TMEs influenced by both spheroid size and the metastatic potential of cancer cells. Furthermore, a high-throughput microfluidic platform equipped with trapping systems and hybrid spheroids was employed to simulate the tumor-immune system of complex TMEs and for comparative analysis with traditional 3D culture models. This study provides insight into TAM polarization in melanoma with different heterogeneities by modeling cancer-immune systems, which can be potentially employed for immune-oncology research, drug screening, and personalized therapy. STATEMENT OF SIGNIFICANCE: This study presents the development of a 3D hybrid spheroid system designed to model tumor-immune interactions, providing a detailed analysis of how melanoma cell metastatic potential influences tumor-associated macrophage (TAM) polarization. By utilizing a microfluidic platform, we are able to replicate and investigate the complex tumor-immune system of the tumor microenvironments (TMEs) under continuous flow conditions. Our model holds significant potential for high-throughput drug screening and personalized medicine applications, offering a versatile tool for advancing cancer research and treatment strategies.

Lung cancer is a major threat to human health and a leading cause of death. Accurate localization of tumors in vivo is crucial for subsequent treatment. In recent years, fluorescent imaging technology has become a focal point in tumor diagnosis and treatment due to its high sensitivity, strong selectivity, non-invasiveness, and multifunctionality. Molecular probes-based fluorescent imaging not only enables real-time in vivo imaging through fluorescence signals but also integrates therapeutic functions, drug screening, and efficacy monitoring to facilitate comprehensive diagnosis and treatment. Among them, near-infrared (NIR) fluorescence imaging is particularly prominent due to its improved in vivo imaging effect. This trend toward multifunctionality is a significant aspect of the future advancement of fluorescent imaging technology. In the past years, great progress has been made in the field of NIR fluorescence imaging for lung cancer management, as well as the emergence of new problems and challenges. This paper generally summarizes the application of NIR fluorescence imaging technology in these areas in the past five years, including the design, detection principles, and clinical applications, with the aim of advancing more efficient NIR fluorescence imaging technologies to enhance the accuracy of tumor diagnosis and treatment.

Endometrial cancer is the most common gynecological malignancy worldwide and unfortunately has a much higher mortality rate in Black women compared with White women. Many potential factors contribute to these mortality rates, including the underlying effects of systemic and interpersonal racism. Furthermore, other trends in medicine have potential links to these rates including participation in clinical trials, hormone therapy, and pre-existing health conditions. Addressing the high incidence and disparate mortality rates in endometrial cancer requires novel methods, such as nanoparticle-based therapeutics. These therapeutics have been growing in increasing prevalence in pre-clinical development and have far-reaching implications in cancer therapy. The rigor of pre-clinical studies is enhanced by the likeness of the model to the human body. In systems for 3D cell culture, for example, the extracellular matrix mimics the tumor more closely. The increasing emphasis on precision medicine can be applied to cancer using nanoparticle-based methods and applied to pre-clinical models by using patient-derived model data. This review highlights the intersections of nanomedicine, precision medicine, and racial disparities within endometrial cancer and provides insights into reducing health disparities using recent scientific advances on the nanoscale.

The objective of this study was to investigate how L1 cell adhesion molecule (L1CAM) interacting with protein tyrosine kinase 2 (PTK2) affects endometrial cancer (EC) progression and determine its association with the focal adhesion kinase (FAK)-growth factor receptor-bound protein 2 (GRB2)-son of sevenless (SOS)-rat sarcoma (RAS) pathway. EC is a female cancer of major concern in the world, and its incidence has increased rapidly in recent years. L1CAM is considered a reliable marker of poor prognosis in patients with EC.

A single-center and prospective study was conducted using data from the Cancer Genome Atlas and samples from normal and EC tissues to explore the differential expression of L1CAM. Additional experimental models included human immortalized endometrial epithelium cells (hEECs) and EC cell lines such as KLE, RL95-2, and Ishikawa. L1CAM expression was regulated using lentiviruses designed for either overexpression or interference, and PTK2/focal adhesion kinase (FAK) signaling was inhibited with PF431396. Transfected KLE cells were injected into mice, and tumor growth was monitored over 14 days. Cellular proliferation and survival were assessed using cell counting kit, colony formation, and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling assays. Metastatic behavior was evaluated through Transwell assays for cell migration and invasion. The expression levels of matrix metallopeptidase (MMP) 2 and MMP9 were determined by Western blot. In addition, the activation of the FAK-GRB2-SOS-RAS pathway was examined by assessing the protein levels of FAK, GRB2, SOS, and RAS.

There was a significant difference in L1CAM expression between EC tumor tissues and normal tissues, and L1CAM messenger RNA (1.85-fold) and L1CAM protein (2.59-fold) were significantly more expressed in EC tissues (P < 0.01) than in normal tissues. The tumor growth of L1CAM overexpressing EC cells was faster than that of negative control EC cells (6.43 fold; P < 0.001). L1CAM promoted the expression of FAK (1.43-2.72-fold; P < 0.001); enhanced EC cell proliferation (P < 0.01), survival and motility (P < 0.001), migration (P < 0.001), and invasion (P < 0.001); and activated the FAK-GRB2-SOS-RAS pathway, all of which were reversed when FAK expression was not upregulated (P < 0.001).

By upregulating PTK2 and its encoded protein FAK, L1CAM was found to promote tumor progression and increase the activation of the FAK-GRB2-SOS-RAS pathway. These findings establish L1CAM and PTK2 as reference genes for poor prognostic prediction in EC and as targets for EC therapy, providing a valuable basis for distinguishing between benign and malignant endometrial conditions and justifying the necessity of targeted therapeutic approaches.

Cancer continues to pose a significant threat to global health, with its high mortality rates largely attributable to delayed diagnosis and non-specific treatments. Early and accurate diagnosis is crucial, yet it remains challenging due to the subtle and often undetectable early molecular changes. Traditional single-target fluorescent probes often fail to accurately identify cancer cells, relying solely on single biomarkers and consequently leading to high rates of false positives and inadequate specificity. In contrast, dual-locked fluorescent probes represent a breakthrough, designed to enhance diagnostic precision. By requiring the simultaneous presence of two specific tumor-associated biomarkers or microenvironmental conditions, these probes significantly reduce non-specific activations typical of conventional single-analyte probes. This review discusses the structural designs, response mechanisms, and biological applications of dual-locked probes, highlighting their potential in tumor imaging and treatment. Importantly, the review addresses the challenges, and perspectives in this field, offering a comprehensive look at the current state and future potential of dual-locked fluorescent probes in oncology.

Diseases of the female reproductive system, especially malignant tumors, pose a serious threat to women's health worldwide. One of the key factors limiting research progress in this area is the lack of representative models. Organoid technology, especially tumor organoids, has been increasingly applied in the study of female reproductive system tumors due to their high heterogeneity, close resemblance to the physiological state, easy acquisition and cultivation advantages. They play a significant role in understanding the origin and causes of tumors, drug screening, and personalized treatment and more. This article reviews the organoid models for the female reproductive system, focusing on the cancer research advancements. It discusses the methods for constructing tumor organoids of the female reproductive tract and summarizes the limitations of current research. The aim is to offer a reference for future development and application of these organoid models, contributing to the advancement of anti-tumor drugs and treatment strategies for female reproductive tract cancer patients.

While lymph node metastasis (LNM) plays a critical role in determining treatment options for endometrial cancer (EC) patients, the existing preoperative methods for evaluating the lymph node state are not always satisfactory. This study aimed to develop and validate a nomogram based on intra- and peritumoral radiomics features and multiparameter magnetic resonance imaging (MRI) features to preoperatively predict LNM in EC patients.

Three hundred and seventy-four women with histologically confirmed EC were divided into training (n = 220), test (n = 94), and independent validation (n = 60) cohorts. Radiomic features were extracted from intra- and peritumoral regions via axial T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) mapping. A radiomics model (annotated as the Radscore) was established using the selected features from different regions. The clinical parameters were statistically analyzed. A nomogram was developed by combining the Radscore and the most predictive clinical parameters. Decision curve analysis (DCA) and the net reclassification index (NRI) were used to assess the clinical benefit of using the nomogram.

Nine radiomics features were ultimately selected from the intra- and peritumoral regions via ADC mapping and T2WI. The nomogram combining the Radscore, serum CA125 level, and tumor area ratio achieved the highest AUCs in the training, test and independent validation sets (nomogram vs. Radscore vs. clinical model: 0.878 vs. 0.850 vs. 0.674 (training), 0.877 vs. 0.838 vs. 0.668 (test), and 0.864 vs. 0.836 vs. 0.618 (independent validation)). The DCA and NRI results revealed the nomogram had greater diagnostic performance and net clinical benefits than the Radscore alone.

The combined intra- and peritumoral region multiparameter MRI radiomics nomogram showed good diagnostic performance and could be used to preoperatively predict LNM in patients with EC.

The occurrence and progression of tumors are linked to the process of pyroptosis. However, the precise involvement of pyroptosis-associated genes (PRGs) in endometrial cancer (EC) remains uncertain. 29 PRGs were identified as being either up-regulated or down-regulated in EC. PRGs subgroup analysis demonstrated distinct survival outcomes and diverse responses to chemotherapy and immune checkpoint blockade therapy. A higher expression of GPX4 and NOD2, coupled with lower levels of CASP6, PRKACA, and NLRP2, were found to be significantly associated with higher overall survival (OS) rates (p < 0.05). Conversely, lower expression of NOD2 was linked to lower progression-free survival (p = 0.021) and advanced tumor stage(p = 0.0024). NOD2, NLRP2, and TNM stages were identified as independent prognostic factors (p < 0.001). The LASSO prognostic model exhibited a notable decrease in OS among EC patients in the high-risk score group (ROC-AUC10-years: 0.799, p = 0.00644). Furthermore, NOD2 displayed a positive correlation with the infiltration of immune cells and the expression of immune checkpoints (p < 0.001). GPX4 and CASP6 are significantly associated with TMB and MSI (RTMB = 0.39; RMSI = 0.23). Additionally, a substantial upregulation of NOD2 was confirmed in both EC cells and tissue, indicating a positive relationship between advanced TNM stage (p < 0.0001) and infiltration of M1 phenotype macrophages. Nonetheless, its impact on patient OS did not reach statistical significance (p = 0.141). Our findings have contributed to the advancement of a prognostic model for EC patients. NOD2 receptor-mediated pyroptosis mechanism potentially regulates tumor immunity and promotes the transformation of macrophages from the M2 phenotype to the M1 phenotype, which significantly impacts the progression of EC.

Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that address this gap in treatment options. Cell-based therapies have gained wide attention as a therapeutic option that could address this gap in treatment options for advanced melanoma. These therapies work by extracting certain cell types produced in the human body such as T-cells, modifying them based on a specific target, and transfusing them back into the patient. In the realm of cancer therapy, cell-based therapies utilize immune cells to target tumor cells while sparing healthy cells. Recently, the Food and Drug Administration (FDA) has approved the usage of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, in advanced melanoma. This came following recent results from the C-144-01 study (NCT02360579), which demonstrated the efficacy and safety of TILs in metastatic melanoma patients who otherwise failed on standard ICI/targeted therapy. Thus, the results of this trial as well as the recent FDA approval have proven the viability of utilizing cell-based therapies to fill the gap in treatment options for patients with advanced melanoma. This review aims to provide a comprehensive overview of major cell-based therapies that have been utilized in melanoma by delineating results of the most recent multi-center phase II/ III clinical trials that evaluate the efficacy and safety of major cell-based therapies in melanoma. Additionally, we provide a summary of current limitations in each cell-based therapeutic option as well as a future direction of how to further extrapolate these cell-based therapies in advanced melanoma.

A systematic review was conducted to investigate differences in incidence and primary origin of synchronous brain metastasis (sBM) in varying racial groups with different primary cancers.

Adhering to PRISMA 2020 guidelines a search was conducted using PubMed and Ovid databases for publications from January 2000 to January 2023, with search terms including combinations of "brain metastasis," "race," "ethnicity," and "incidence." Three independent reviewers screened for inclusion criteria encompassing studies clearly reporting primary cancer sites, patient demographics including race, and synchronous BM (sBM) incidence.

Of 806 articles, 10 studies comprised of mainly adult patients from the United States met final inclusion for data analysis. Higher sBM incidence proportions were observed in American Indian/Alaska native patients for primary breast (p < 0.001), colorectal (p = 0.015), and esophageal cancers (p = 0.024) as well as in Asian or Pacific islanders for primary stomach (p < 0.001), thyroid (p = 0.006), and lung/bronchus cancers (p < 0.001) yet higher proportions in White patients for malignant melanoma (p < 0.001). Compared to White patients, Black patients had higher sBM incidence likelihood in breast cancer (OR = 1.27, p = 0.01) but lower likelihood in renal (OR = 0.46, p < 0.001) and esophageal cancers (OR = 0.31, p = 0.005). American Indian/Alaska native patients had a higher sBM likelihood (OR = 3.78, p = 0.004) relative to White patients in esophageal cancer.

These findings reveal several comparative racial differences in sBM incidence arising from different primary cancer origins, underscoring a need for further research to explain these variations. Identifying the factors contributing to these disparities holds the potential to promote greater equity in oncological care according to cancer type.

This study tested the hypothesis that our predominately AA medical center population would demonstrate a decline in HCV-driven HCC diagnosis following the initiation of DAA treatment in 2014. Also evaluated was whether achieving an SVR prior to diagnosis of HCC improved outcomes in patients who had an HCV diagnosis after completion of treatment.

All patients with HCC seen at the Detroit Medical Center from 2009 to 2021 were identified using ICD-10 codes, and medical records were evaluated. Outcomes were evaluated as either alive or death/hospice as of December of 2022.

There were 461 patients with HCC of whom 433 (94%) had racial information in the database (AA = 351; non-AA = 82). HCC incidence regardless of race peaked in 2017, with a subsequent decline through 2021. HCV as a risk factor was higher in AA as compared to non-AA (85% vs. 53% p = 0.0001). Outcome (alive vs. death/hospice) was better for SVR patients compared to untreated patients (54% vs. 19%; p = 0.0009). HCC patients who achieved SVR also had better liver function at diagnosis as defined by Child-Pugh score (74% vs. 49% Class A p = 0.04) at the time of diagnosis.

Racial disparity in HCC etiology was confirmed with AA more likely to have HCV than non-AA. The reduction in HCC patients with HCV confirms the impact of DAA treatment and prior successful treatment of HCV yields better outcomes. Increasing HCV treatment rates especially in AA patients will have a major impact on HCC development and treatment outcomes.

• African Americans are more likely to have HCV infection as compared to non-AA. • Hepatocellular carcinoma is increasing in incidence in the US. • The role of HCV in the development of HCC remains to be further investigated.

• HCC diagnosis in a single urban medical center study increased from 2009 as a result of HCV as a risk factor. • HCC declined post 2018 due primarily to a reduction in HCV infection as the risk factor. • African Americans were more likely to have HCV as the risk factor as compared to non-AA patients who were more likely to have no known risk factor on record (i.e., cryptogenic).