Radioisotope-labeled prostate-specific membrane antigen (PSMA) PET tracers have gained popularity in diagnosing prostate cancer (PCa). Recently, a novel biphenyl-containing tracer [68Ga]Ga-PSMA-D5 targeting PSMA has been developed for PET imaging of PCa. The advantages of [68Ga]Ga-PSMA-D5 include high tumor uptake, simple synthesis, and convenient labeling, making it a promising PSMA PET tracer. In order to facilitate the routine production and clinical application of [68Ga]Ga-PSMA-D5, a straightforward and efficient automated synthesis is described. The optimum labeling parameters were determined at laboratory scale, and subsequently incorporated into an automated production process. Further studies have demonstrated that clinical doses of [68Ga]Ga-PSMA-D5 can be prepared within 25 min, with excellent radio chemical purity (>99 %) and activity yield (70.8 % ± 2.3 %, non-decay corrected). All the quality control results satisfy the required criteria for release. PET/CT imaging has shown that [68Ga]Ga-PSMA-D5 can safely and effectively target prostate cancer-associated lesions with excellent tumor-to-background contrast. This methodology facilitates efficient synthesis of [68Ga]Ga-PSMA-D5 in a commercially available synthesis module and shows diagnostic value for PCa in further clinical application.

Gossypin, a flavone found in Hibiscus vitifolius, exhibits antioxidant, antidiabetic, anti‑inflammatory and anticancer effects. The present study investigated the potential of gossypin to induce apoptosis and autophagy in HT‑29 human colorectal cancer (CRC) cells, and assessed its association with the MAPK/JNK pathway. Cell viability assays, DAPI staining, flow cytometry, acridine orange staining, western blotting, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and immunohistochemistry were performed. The results revealed an increased number of apoptotic bodies, higher apoptosis rates and enhanced autophagy in gossypin‑treated HT‑29 cells. To investigate autophagy during cell death, the effects of the early autophagy inhibitor 3‑methyladenine (3‑MA) and the late autophagy inhibitor hydroxychloroquine on cell viability and the expression of apoptosis‑related proteins were assessed. Significant increases in cell viability were observed following 3‑methyladenine pretreatment, as well as a decrease in the expression levels of Bcl‑2 and an increase in Bax. The analysis of MAPK pathway proteins following treatment with gossypin revealed that the levels of phosphorylated (p‑)JNK and p‑p38 were significantly increased in a concentration‑dependent manner. The JNK inhibitor SP600125 was used to confirm the role of the JNK pathway in gossypin‑induced apoptosis and autophagy. Moreover, gossypin reduced the volume of HT‑29 tumors in mice, and western blotting indicated the induction of apoptosis and autophagy in these tumors in vivo. Finally, TUNEL and immunohistochemistry experiments confirmed the induction of apoptosis and p‑JNK upregulation in these tumors in vivo. In conclusion, the present study suggested that gossypin may induce MAPK/JNK‑mediated apoptosis and autophagy in HT‑29 CRC cells, highlighting the potential of gossypin as an anticancer agent.

Sex and gender have emerged as central modifiers of disease biology, phenotype, and clinical outcomes in myeloproliferative neoplasms (MPNs). This review will uniquely highlight issues affecting women with MPN and articulate their relevant determinants.

A higher overall prevalence of MPN has been established in women. The incidence of essential thrombocythemia (ET) predominates, while, conversely, polycythemia vera (PV) and myelofibrosis (MF) are seen in lower frequencies as compared to men. Diagnostic criteria are dictated by sex-driven physiological variances in hemoglobin and hematocrit levels in PV, mandating separate diagnostic thresholds, respectively: > 16.0 g/dL and > 48% in women vs. > 16.5 and > 49% in men.

Women with MPN harbor fewer acquired somatic mutations and a lower frequency of high-risk mutations than their male counterparts; lower JAK2V617F driver variant allele frequency and attenuated allele burden kinetics have also been reported. Women with MPN are younger at diagnosis than men and, contingent on subtype, display more indolent disease features. Importantly, validated symptom burden assessments consistently disclose higher scores in women vs. men.

Women with MPN have a unique thrombotic diathesis with respect to men, more frequently involving the splanchnic venous system in those ultimately diagnosed with PV. Outcomes data depict female sex as a variable associated with more favorable clinical trajectories, including lower rates of MF/leukemic transformation and secondary cancers, as well as improved overall survival rates vis-à-vis men.

Potential challenges at each significant life stage will be addressed: puberty, preconception and fertility, and perimenopause; these include issues surrounding oral contraceptives and hormone use. Prospective studies suggest overall favorable maternal and fetal outcomes with pregnancy in women with MPN. Full details on risks and reported outcomes will be discussed, as well as a risk-adapted approach to management informed by obstetric and thrombosis history. Recommendations include aspirin 81 mg daily in all patients and cytoreduction with interferon-α in those with antecedent thrombosis, as well as in low-risk cases with higher-risk features (e.g., poorly controlled hematocrit and recurrent fetal loss). Antepartum anticoagulation with low molecular weight heparin (LMWH) is recommended in cases with previous venous thromboembolism.

This review highlights female sex and gender as critical drivers of MPN incidence, presentation, and natural history. It further outlines the impact and management of MPN as related to unique female reproductive phases. A sex-informed lens will be required in order to recalibrate current prognostic tools, a requisite to refining patient counselling and clinical decision-making in line with precision medicine. Moreover, while several mechanisms underpinning sex-defined discrepancies have been defined, these mandate further prospective study. Finally, sex and gender-based differences must be weighted in clinical trials with systematized procedures to correct participation imbalances in favor of sex and gender equity.

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.

A diet rich in fruits, vegetables, coffee, and tea, limited red meat, and moderate alcohol intake may reduce the risk of renal cell carcinoma (RCC). The anti-inflammatory potential of diet has been proposed as a mechanism influencing cancer risk. This study assessed the association between an anti-inflammatory diet and RCC risk.

Data from two Swedish cohorts, the Swedish-Mammography-Cohort and the Cohort-of-Swedish-Men, were analysed. Dietary habits were assessed using a 96-item food frequency questionnaire. The Anti-Inflammatory Diet Index (AIDI), composed of 16 food groups (11 anti-inflammatory and 5 pro-inflammatory), was used to score dietary patterns. RCC cases were identified from the Swedish Cancer Register using ICD-10 codes, and Cox proportional hazards models were used to estimate hazard ratios based on AIDI quartiles.

Among 71,421 participants, 431 RCC cases were identified during a 19.7-year follow-up. Higher AIDI scores were associated with a lower RCC risk (HR for Q4 vs. Q1: 0.68, CI: 0.52-0.89). In sex-stratified analyses (p-for heterogeneity = 0.006), the association was stronger in among women (HR: 0.47, CI: 0.30-0.75) but less clear in among men (HR: 0.83, CI: 0.63-1.24).

These data suggest that adherence to an anti-inflammatory diet may confer a reduced risk for RCC, especially among women.

Underweight women and those with obesity, defined as having a body mass index (BMI) ≥ 30 kg/m2, diagnosed with breast cancer (BC) are known to have worse prognosis. Whether BMI impacts BC stage at diagnosis and BC specific survival (BCSS) is not understood. We aim to better understand the relationship between BMI with stage at BC diagnosis and BCSS.

Women age ≥ 15 years old diagnosed with BC between 2014 and 2019 were identified from the California Cancer Registry. BMI at diagnosis was classified as underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity class 1-2 (30-39.9 kg/m2), and obesity class 3 (≥ 40 kg/m2). BC late stage of diagnosis was defined as American Joint Committee on Cancer stage 3 and 4. Multivariate logistic regression was performed to compare sociodemographic and clinical factors associated with late stage. Multivariable cox proportional hazards regression models assessed association of BMI and BCSS.

Of 159,248 patients: 2.2% were underweight, 34.6% normal weight, 30.5% overweight, 26.7% obesity class 1-2, and 6.0% obesity class 3. Compared to normal weight, patients who were underweight [Hazard Ratio (HR) 1.54, 95% Confidence Interval (CI) 1.51-1.57], obesity class 1-2 [HR 1.06, 1.05-1.07], and obesity class 3 [HR 1.14, 1.12-1.16] were more likely to be diagnosed with late-stage BC. In models stratified by age, patients ≥ 40 years who were underweight had worse BCSS, while patients ≥ 51 years with obesity class 1-2 had better BCSS.

Patients with obesity class 1-2 were more likely to be diagnosed with a later stage, but had improved BCSS, supporting an "obesity paradox" in BC and suggesting that other measures are needed to better assess body composition, adipose distribution, and metabolic health of patients. Patients who were underweight had worse survival, suggesting this high-risk group may benefit from being assessed and treated for possible sarcopenia and malnourishment.

Globally, the incidence and death rates associated with cancer persist in rising, despite considerable advancements in cancer therapy. Although some malignancies are manageable by a mix of chemotherapy, surgery, radiation, and targeted therapy, most malignant tumors either exhibit poor responsiveness to early identification or endure post-treatment survival. The prognosis for prostate cancer (PCa) is unfavorable since it is a perilous and lethal malignancy. The capacity of phytochemical and nutraceutical chemicals to repress oncogenic lncRNAs and activate tumor suppressor lncRNAs has garnered significant attention as a possible strategy to diminish the development, proliferation, metastasis, and invasion of cancer cells. A potential technique to treat cancer and enhance the sensitivity of cancer cells to existing conventional therapies is the use of phytochemicals with anticancer characteristics. Functional studies indicate that lncRNAs modulate drug resistance, stemness, invasion, metastasis, angiogenesis, and proliferation via interactions with tumor suppressors and oncoproteins. Among them, numerous lncRNAs, such as HOTAIR, PlncRNA1, GAS5, MEG3, LincRNA-21, and POTEF-AS1, support the development of PCa through many molecular mechanisms, including modulation of tumor suppressors and regulation of various signal pathways like PI3K/Akt, Bax/Caspase 3, P53, MAPK cascade, and TGF-β1. Other lncRNAs, in particular, MALAT-1, CCAT2, DANCR, LncRNA-ATB, PlncRNA1, LincRNA-21, POTEF-AS1, ZEB1-AS1, SChLAP1, and H19, are key players in regulating the aforementioned processes. Natural substances have shown promising anticancer benefits against PCa by altering essential signaling pathways. The overexpression of some lncRNAs is associated with advanced TNM stage, metastasis, chemoresistance, and reduced survival. LncRNAs possess crucial clinical and transitional implications in PCa, as diagnostic and prognostic biomarkers, as well as medicinal targets. To impede the progression of PCa, it is beneficial to target aberrant long non-coding RNAs using antisense oligonucleotides or small interfering RNAs (siRNAs). This prevents them from transmitting harmful messages. In summary, several precision medicine approaches may be used to rectify dysfunctional lncRNA regulatory circuits, so improving early PCa detection and eventually facilitating the conquest of this lethal disease. Due to their presence in biological fluids and tissues, they may serve as novel biomarkers. Enhancing PCa treatments mitigates resistance to chemotherapy and radiation.

Bevacizumab was the first targeted therapy developed for newly diagnosed and recurrent advanced ovarian cancer (AOC). Although bevacizumab has been approved for the treatment of AOC for several years, identifying patients who may benefit most from this treatment is still debated. Bevacizumab has been associated with improved progression-free survival (PFS) regardless of clinical risk, but in some countries the use of bevacizumab in the treatment of newly diagnosed AOC has been restricted to higher-risk patients (stage III inoperable or suboptimally debulked disease, or stage IV disease); this is primarily due to the findings of exploratory subgroup analyses from phase III trials that suggest only higher-risk patients derive an overall survival (OS) advantage with bevacizumab. Recently reported post hoc analyses from the PAOLA-1 trial of maintenance olaparib plus bevacizumab versus bevacizumab alone for patients with newly diagnosed AOC and homologous recombination deficiency-positive tumors suggested PFS and OS benefit was achieved in both lower-risk (with stage III disease who had undergone upfront surgery and had complete resection) and higher-risk (with stage III disease who had undergone upfront surgery and had residual disease or who had received neoadjuvant chemotherapy, or with stage IV disease) patients, prompting reassessment of the role of bevacizumab in lower-risk patients. This review examines the role of bevacizumab in the AOC treatment pathway by discussing its efficacy and safety in the first-line, maintenance and recurrent settings, and evaluates the clinical implications of bevacizumab use across risk groups and lines of therapy.

The pachysandra alkaloids found in Sarcococca ruscifolia demonstrate notable anti-hepatocellular carcinoma activity. Despite their efficacy, the structural diversity of these compounds remains limited, and their precise antitumor mechanism is still unclear. In pursuit of identifying novel lead compounds with high efficacy and low toxicity for combating hepatocellular carcinoma, twenty-three compounds of C20-ketone pachysandra alkaloid derivatives were designed and synthesized by using 3-dimethylamine pachysandra alkaloids as scaffolds. Subsequent in vitro anticancer activity experiments showed that synthetic pachysandra alkaloids had a stronger effect on HepG2 cells than did their natural counterparts, with low toxicity and high selectivity. The most potent derivative, 6k, had an IC50 value of 0.75 μM, demonstrating 25.7-fold greater anticancer activity than sarcovagine D against HepG2 cells. Through network pharmacology and molecular docking analysis, it was revealed that synthetic pachysandra alkaloids may exert their effects by inhibiting the JAK2/STAT3 pathway, thereby preventing the proliferation of liver cancer cells. Further research through scratch tests, immunofluorescence experiments, and Western blot analysis revealed that compound 6k effectively inhibited the migration of HepG2 cells and induced mitochondria-mediated intrinsic apoptosis of HepG2 cells by regulating the JAK2/STAT3 signaling pathway. The aforementioned results indicate that compound 6k could be developed as a potential candidate for the treatment of hepatocellular carcinoma.

Targeting more than one in nine men before age 70, prostate cancer is the most common type of cancer in men. The increased levels of cyclins, leading to activation of cyclin-dependent kinases (CDKs), play a critical role in the increased proliferation of prostate cancer cells. In this study, the regulation of the cyclin D1 (CCND1) promoter activity by activator protein-1 (AP-1) and SRY-related HMG-box (SOX) transcription factors has been characterized in PC3 prostate cancer cells. The SOX and AP-1 transcription factors can cooperate to activate the CCND1 promoter in PC3 prostate cancer cells and such cooperation can be enhanced by protein kinase A (PKA) and/or mitogen-activated protein kinase kinase 1 (ERK kinase 1, MAP2K1) signaling pathways. Moreover, anacardic acid analogs have been assessed for their potential in reducing cell viability and CCND1 promoter activity. The anacardic acid analog 8b, obtained from γ-resorcylic acid, reduces the viability and proliferation of PC3 cells by decreasing CCND1 promoter activity. The effect of analog 8b, which perfectly mimics the structure of anacardic acid, can be attributed to the inhibition of the activities of the transcription factors SOX and AP-1, which are important regulators of CCND1 promoter activity in prostate cancer cells.

The stage at which Colorectal cancer (CRC) diagnosed is a crucial prognostic factor. Our study proposed a novel approach to aid in the diagnosis of stage IV CRC by utilizing supervised machine learning, analyzing clinical history, and laboratory values, comparing them with those of stage I CRC.

We conducted a respective study using patients diagnosed with stage I (n = 433) and stage IV CRC (n = 457). We employed supervised machine learning using random forest. The decision tree is used to visualize the model to identify key clinical and laboratory factors that differentiate between stage IV and stage I CRC.

The decision tree classifier revealed that symptoms combined with laboratory values were critical predictors of stage IV CRC. Change in bowel habits was predictive for stage IV CRC among 14 of 22 patients (63 %). Weight loss, constipation, and abdominal pain in combination with different levels of carcinoembryonic antigen (CEA) were predictors for stage IV CRC. A CEA level higher than 260 was indicative for stage IV CRC in all observed patients (61 out of 61 patients). Additionally, a lower CEA level, in combination with hemoglobin, white blood cell count, and platelet count, also predicted stage IV CRC.

By applying a machine learning based approach, we identified symptoms and laboratory values (CEA, hemoglobin, white blood cell count, and platelet count), as crucial predictors for stage IV CRC diagnosis. This method holds potential for facilitating the diagnosis of stage IV CRC in clinical practice, even before imaging tests are conducted.

With the increase in life expectancy, age-related conditions and diseases have become a widespread and relevant social burden. Among these, immunosenescence and cancer cachexia play a significant often intertwined role. Immunosenescence is the progressive aging decline of both the innate and adaptive immune systems leading to increased infection susceptibility, poor vaccination efficacy, autoimmune disease, and malignancies. Cancer cachexia affects elderly patients with cancer causing severe weight loss, muscle wasting, inflammation, and reduced response to therapies. Whereas the connections between immunosenescence and cancer cachexia have been raising attention, the molecular mechanisms still need to be completely elucidated. This review aims at providing the current knowledge about the interplay between immunosenescence, skeletal muscle, and cancer cachexia, analyzing the molecular pathways known so far to be involved. Finally, we highlight potential therapeutic strategies suited for elderly population aimed to block immunosenescence and to preserve muscle mass in cachexia, also presenting the analysis of the current state-of-the-art of related clinical trials.

Prostate, bladder, and kidney cancers represent the three most prevalent genitourinary malignancies, posing substantial global health burdens. Given the limited epidemiological research on early-onset genitourinary cancers (EOGCs), this study aims to investigate the temporal trends and health disparities in EOGCs from 1990 to 2021.

Based on the Global Burden of Disease Study 2021 (GBD), we extracted data on the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of the three major genitourinary cancers (prostate, bladder, kidney cancer) among individuals aged 15 to 49. We described the distribution of EOGCs at the global, regional and national levels, and analyzed the overall and local time trends through the estimated annual percentage change (EAPC) and joinpoint regression. Spearman's test and health inequality analysis were used to examine the relationship between the disease burden of EOGCs and the Socio-demographic Index (SDI).

In 2021, the incident cases of early-onset kidney cancer (EOKC), early-onset bladder cancer (EOBC), and early-onset prostate cancer (EOPC) were 52,631, 31,054, and 17,865, respectively, with 10,978, 6,328, and 2,861 death cases. The most significant attributable risk factors for EOGC-related deaths and DALYs were smoking and high body mass index. Of particular note, male EOKC consistently demonstrated the highest age-standardized incidence rate (ASIR) and mortality rate (ASMR), with both metrics exhibiting sustained increases from 1990 to 2021, corresponding to EAPCs of 1.33% and 0.3%, respectively. The disease burdens of EOGCs were distributed differently across various regions and countries, and their local trends also varied during the period from 1990 to 2021 globally. The incidence burden of EOGCs was disproportionately concentrated in high-SDI countries, with the concentration indices of EOPC, EOBC and EOKC in 2021 being 0.26, 0.17 and 0.27 respectively. Notably, in regions or countries with a higher SDI, the incidence risk of EOGCs was relatively high, but the mortality risk decreased significantly.

EOGCs are a major global public health challenge. There is an urgent need for personalized healthcare strategies to alleviate the burden of genitourinary cancers, particularly kidney cancer and prostate cancer, among adolescents and adults.

The aim of this study was to retrospectively investigate the efficacy of chemotherapy for neck lymph node metastasis (NLNM) by determining the characteristics and survival of patients with isolated NLNMs metastases from epithelial ovarian carcinoma (EOC) at stage IV of the Federation of Gynecology and Obstetrics (FIGO).

The clinicopathological characteristics and survival outcome of 24 cases with stage IV FIGO EOC with isolated NLNM were retrospectively analyzed between December 1, 2014, and November 30, 2021.

Among the 24 patients, 2 (8.3%) underwent primary debulking surgery (PDS), 21 (87.5%) received neoadjuvant chemotherapy(NACT) followed by interval debulking surgery (IDS), and 1 (4.2%) received chemotherapy alone. Additionally, 13 (54.2%) cases achieved abdominal R0 debulking, while 11(45.8%) cases achieved R1/R2 debulking. The chemotherapy response of NLNMs included complete response (8/24, 33.3%), partial response (15/24,62.5%), or stable disease (1/24,41.7%). None of the patients received resection or radiotherapy of NLNMs. Recurrence was observed in 15 (62.5%) patients, with only 2 experiencing recurrence of NLNMs. The median progression-free survival (PFS) and overall survival (OS) were 35 months and 48 months, respectively. R0 debulking led to a significantly longer PFS (not reached) and OS (57 months) compared to non-R0 debulking (PFS: 10 months, P = 0.001; OS: 22 months, P = 0.001). Interestingly, patients with EOC with lymphatic recurrence had better OS ( 57 months) than did those with abdominal or distant recurrence (OS: 29 months; P = 0.012).

Chemotherapy is an effective treatment for neck lymph nodes metastasis, and a favorable response to chemotherapy could eliminate the necessity for NLNM resection or radiotherapy. Effective control of abdominal disease with surgery may be a critical factor in managing FIGO stage IV EOC patients with isolated NLMNs.

GPRC5D is a promising myeloma-associated antigen, and several GPRC5D-targeted therapies are under active investigation, including CAR T cells, bispecific and trispecific antibodies, and antibody-drug conjugates. This class of agents is poised to transform the landscape of multiple myeloma treatment.

Here, we review the biology of GPRC5D, the current and emerging uses of talquetamab in relapsed/refractory multiple myeloma, the landscape of investigational GPRC5D-targeted drugs, and how these agents are likely to be implemented into future clinical practice.

Talquetamab is currently the only approved GPRC5D-targeted therapy, primarily used for BCMA-refractory multiple myeloma, but there is no biological reason BCMA therapies must be exhausted before targeting GPRC5D; utilizing GPRC5D in innovative ways will be key to fully realizing its therapeutic potential. Newer trials are exploring more aggressive approaches combining multiple immunotherapy targets within a single line to prevent resistance and potentially achieve a cure. While GPRC5D-targeted therapies are highly effective, they also pose significant toxicity risks including oral, skin, nail, and cerebellar toxicity. In addition to improving efficacy, future research must also focus on optimizing dosing, identifying biomarkers for toxicity, and developing better strategies for managing adverse events to optimize the risk-benefit profile of these therapies.

PIWI-interacting RNAs (piRNAs), a novel category of small non-coding RNAs, are widely expressed in eukaryotes and deregulated in several pathologies, including cancer. Little is known about their function and mechanism in renal cell carcinoma (RCC) progression. Herein, a down-regulated piRNA in RCC, termed piR-hsa-28489 (designated as piR-RCC), is identified to impede RCC progression both in vivo and in vitro. Mechanistically, piR-RCC directly interacts with Y-box binding protein 1 (YBX-1), thus impeding p-AKT-mediated YBX-1 phosphorylation and its subsequent nuclear translocation. Moreover, YBX-1 coordinates the transcription of ETS homologous factor (EHF) as a repressor factor. Consequently, piR-RCC enhances EHF expression, leading to the inhibition of RCC proliferation and metastasis. Based on these, a biomimetic nanoparticle platform is constructed to achieve RCC-specific targeted delivery of piR-RCC. The nanoparticles are fabricated using a cell membrane coating derived from cancer cells and used to encapsulate and deliver piR-RCC plasmids to renal orthotopic implantation in mice, hindering RCC progression. This study illustrates piR-RCC/YBX-1/EHF signaling axis in RCC, offering a promising therapeutic avenue for RCC.

The number of gastrointestinal (GI) cancer survivors has increased substantially due to improvements in early detection and treatment, yet long-term functional patient outcomes remain poorly characterized. We sought to quantify the burden of activity limitations (AL) and functional limitations (FL) among GI cancer survivors compared with non-GI cancer survivors and the general U.S. population, as well as identify key predictors of cancer-related limitations.

The National Health Interview Survey (NHIS), a nationally representative dataset (1997-2023), was queried to examine the prevalence and trends of cancer-related limitations among GI cancer survivors, non-GI cancer survivors, and the general U.S.

Multivariable logistic regression analyses identified independent predictors of AL and FL, adjusting for demographic and socioeconomic variables.

Among 5,513 GI cancer and 39,887 non-GI cancer survivors, 50.2% (Relative Risk [RR]: 1.23, 95% CI: 1.19-1.27) and 70.7% (RR: 1.07, 95% CI: 1.05-1.09) of GI cancer survivors reported AL and FL, respectively, compared with non-GI cancer survivors. The general U.S. population had a markedly lower prevalence of AL (13.5%; RR: 0.33, 95% CI: 0.33-0.34) and FL (35.7%; RR: 0.54, 95% CI: 0.53-0.54). GI cancer survivors were older (mean age: 69.1 vs. 65.3 vs. 36.1 years), more often single (8.8% vs. 8.6% vs. 28.3%), and more frequently received public insurance (75.1% vs. 68.9% vs. 27.4%) compared with non-GI cancer survivors and the general population (p < 0.05). In multivariable analysis, GI cancer survivors had 21% higher odds of AL (OR: 1.21, 95% CI: 1.11-1.32, p < 0.001) and 11% higher odds of FL (OR: 1.11, 95% CI: 1.00-1.19, p = 0.049).

GI cancer survivors face a significantly higher burden of functional limitations, influenced by demographic and socioeconomic factors.

Addressing functional disparities through targeted rehabilitation and support services may improve long-term outcomes.

Nonmelanoma skin cancer (NMSC), accounts for approximately 90% of skin cancers. Global incidence is rising, with projections showing a significant increase in cases and disability-adjusted life years (DALYs). However, research on NMSC in the Middle East and North Africa (MENA) region is limited. This study aims to assess the epidemiology and burden of NMSC in the MENA region from 1990 to 2021, by sex, age, and socio-demographic index (SDI). The analysis used data from the Global Burden of Disease 2021 on age-standardized rates and cases of incidence, prevalence, deaths, and DALYs. Estimation of NMSCs death was performed by the Cause of Death Ensemble model, while DisMod-MR 2.1 was used for non-fatal outcomes. Counts and rates were presented with 95% uncertainty intervals. In 2021, the MENA region reported an age-standardized incidence rate of 6.7 per 100,000 population for NMSC, a 14% decrease from 1990. However, the age-standardized death rate increased by 10.5% to 0.3, and the DALY rate increased by 8.2% to 4.9 per 100,000. Among the countries, Turkey had the highest age-standardized DALY rate of 13.5 and the Syrian Arab Republic had the lowest with 0.1 per 100,000. Most cases of the disease were observed in older age groups, especially men aged 65-69 and women aged 60-64. Men had higher incidence, mortality, and DALYs than women in all age groups. From 1990 to 2021, the burden of NMSC increased with increasing SDI. There is variations in the NMSC burden in the MENA region. Interdisciplinary education, policy changes, and healthcare improvements are essential to reduce the burden and incidence of NMSCs in the coming years, particularly in the elderly and high SDI countries.

Bladder cancer (BCa) is a leading malignancy in the urinary tract system, often resulting in poor prognosis due to rapid relapse and metastasis, with a low 5-year survival rate. Although the role of N6-methyladenosine (m6A) methylation and long noncoding RNAs (lncRNAs) is implicated in BCa progression, research on how lncRNAs influence BCa prognosis and potential therapeutic interventions remains scarce.

RNA expression profiles and gene mutations for 406 BCa patients were retrieved from the The Cancer Genome Atlas (TCGA) database. A comprehensive dataset was established to correlate lncRNAs with 21 identified m6A-associated genes, categorized into writers, erasers, and readers. Pearson correlation analysis between these m6A genes and lncRNAs was performed and a prognostic model derived from m6A-associated lncRNAs was developed. Immune infiltration was analyzed using multiple evaluative methods and the correlation between single nucleotide variant (SNV) mutations and drug sensitivity was assessed for the correlative relationship with the m6A-associated lncRNA-derived risk scores.

We identified 3,462 m6A-associated lncRNAslinked to BCa prognosis, of which 238 lncRNAs showed significant associations with overall survival in BCa patients. A m6A-associated lncRNA-derived risk model comprising 26 selected lncRNAs was developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, where BCa patients with higher m6A-associated lncRNA-derived risk scores had poorer outcomes. The prognostic significance and reliability was validated, with an area under the curve (AUC) value exceeding 0.7 at multiple time points. Additionally, a nomogram integrating clinical features and m6A-associated lncRNA-derived risk scores had enhanced prognostic accuracy over other clinical indicators, with promise for clinical decision-making. A negative correlation was observed between m6A-associated lncRNA-derived risk scores and tumor mutational burden (TMB). Moreover, patients with high m6A-associated lncRNA-derived risk score group showed significant enrichment of regulatory T cells (Tregs), M2 macrophages, and fibroblasts, highlighting the potential involvement of immune and stromal cells in these BCa patients.

These findings highlight the prognostic value and clinical relevance of m6A-associated lncRNAs in BCa for future patient stratification and personalized therapy approaches.

Diffuse large B-cell lymphoma (DLBCL) presents a substantial clinical challenge due to its aggressive nature and resistance to conventional therapies, thereby developing novel treatment strategies is critical. In this work, we take advantage of the insensitivity of heat shock protein (HSP) expression in senescent tumor cells to combine mild photothermal therapy (MPTT) for efficient DLBCL treatment. Insensitivity to HSPs implies that cells are less capable of activating their usual stress protection mechanisms during MPTT, which reduces their tolerance to heat damage. Consequently, the treatment can more effectively destroy target cells at lower temperatures while minimizing the risk of thermal injury to surrounding healthy tissues. Abemaciclib can inhibit CDK4/6 activity, thereby inhibiting Rb phosphorylation to suppress the activity of the E2F transcription factor and prevent the transition from G1 to S phase, leading to cell cycle arrest and ultimately cellular senescence. The experimental results indicated that abemaciclib effectively promoted the senescence of DLBCL cells, accompanied by a significant reduction in HSP70 expression. Subsequently, a novel near-infrared (NIR) absorbing organic polymer photothermal agent (PYIT-OD) with excellent optical properties and photostability was used for MPTT. The integration of pro-senescence strategies with MPTT, as evidenced by both in vitro and in vivo experimental outcomes, markedly enhanced treatment efficacy, effectively reducing damage to normal tissues at mild temperatures and enhancing antitumor effects. This work not only reveals potential biological mechanisms but also provides theoretical foundations and practical guidance for developing more precise and less toxic DLBCL treatment regimens in clinical practice.

Osteosarcoma (OS) is a prevalent form of bone cancer among younger people, particularly children and adolescents. Ferroptosis is a non-apoptotic cell death identified by increased levels of iron-dependent lipid peroxidation. This study was designed to develop a prognostic model based on differentially expressed genes (DEGs) associated with ferroptosis and examined the functions of ferroptosis-related genes (FRGs) in OS cells. Gene expression profiles in OS were retrieved from TARGET and GEO databases, while GTEx provided data for healthy tissues. Prognostic genes were identified through bioinformatics analysis and data integration. In vitro experiments, cell cultures, qRT-PCR, immunohistochemistry (IHC), cell transfection, Edu assays, DHE assays, migration, and invasion assays validated the prognostic model and explored the functional role of FRGs in OS cells. Univariate Cox regression analysis demonstrated that 12 DEGs were differentially expressed. Based on four FRGs in OS constructed a risk-scoring model. The high-risk (HR) group showed a considerably lower OS rate than the low-risk (LR) group (p < 0.001 in the TARGET and p < 0.05 in the GSE21257 cohorts). A risk score was validated as an independent predictive factor for OS via multivariate Cox regression. Functional analysis shows that these FRGs affect the occurrence of ferroptosis by influencing the intracellular ROS levels and play a regulatory role in the proliferation, migration, and infiltration of OS cells. The findings suggested that four FRGs demonstrate significant prognostic value in OS, offering potential insights into novel therapeutic targets for OS treatment.

Background and Objectives: Prostate cancer (PCa) is a common disease, with a significant number of patients initially diagnosed with locoregional or distant metastases. This is why it is essential to have imaging tests with sufficient sensitivity and specificity. Given the recognized limitations of traditional imaging methods, PSMA-PET has emerged as a promising tool that may revolutionize the management of PCa. Material and Methods: We conducted a comprehensive literature review from August to October 2023 using databases and a review of key clinical guidelines on the topic, focusing on the sensitivity and specificity of PSMA-PET, its use in detecting lymph node metastases (LNm), its integration into nomograms, its comparison with conventional imaging and current guideline recommendations. Results: After considering the search strategy, as well as the inclusion and exclusion criteria, four articles and five guidelines were particularly considered in this review. Most of them suggest high specificity and limited sensitivity for 68Ga-PSMA-PET, with increased detection rates compared to conventional imaging modalities, especially in high-risk PCa patients. However, it cannot replace an extended pelvic lymph node dissection (ePLND) at this time. Conclusions: Although the enhanced sensitivity and specificity of PSMA-PET relative to conventional imaging modalities offers a more precise evaluation of disease extent, prospective studies demonstrating a survival benefit are currently lacking; therefore, caution is advised when making therapeutic decisions.

Endometrial cancer (EC) is the 6th most common cancer among women worldwide. No effective non-invasive screening methods or approved blood biomarkers for EC exist. Previous research explored Attenuated Total Reflection-Fourier Transform Infrared (ATR-FtIR) and Raman spectroscopies, using dried blood plasma. Fresh, 'wet', blood samples, that might provide faster results, have not been investigated. This study compared ATR-FtIR and Raman spectroscopies on 'wet' and dry blood plasma samples for EC detection. It also conducted a preliminary exploration into their diagnostic potential for EC in high-risk individuals with polycystic ovary syndrome (PCOS).

'Wet' and dry blood plasma samples from participants with EC, PCOS and healthy controls were analysed using ATR-FtIR and Raman spectroscopies. Machine learning algorithms and multivariate statistical analyses assessed spectral variance across datasets to evaluate the techniques' diagnostic performance.

Raman analysis of 'wet' plasma achieved 82% accuracy in detecting EC, while ATR-FtIR spectroscopy reached 78%. When combined, diagnostic accuracy reached 86%. In comparison, dry plasma analysis with ATR-FtIR detected EC with 83% accuracy. Spectral similarities were found between EC and PCOS.

Our study suggests that ATR-FtIR and Raman spectroscopies could revolutionise early diagnosis of EC. More research is required to validate these promising findings.

Young-onset colorectal cancer (YOCRC) refers to colorectal cancer diagnosed in individuals under the age of 50. Whilst the overall incidence of colorectal cancer is decreasing, YOCRC cases are increasing and now accounts for up to 10% of all colorectal cancers. YOCRC more frequently presents with acute symptoms, where radiologists play an important role in identifying malignancy and distinguishing it from benign colonic pathologies. Risk factors associated with YOCRC, such as inflammatory bowel disease and hereditary syndromes, may exhibit specific imaging manifestations. In addition, YOCRC is frequently associated with a mucinous histopathological subtype which may be identifiable based on the presence of specific imaging features. Given their younger age, these patients are more likely to undergo aggressive treatment and complex surgical interventions. Specific considerations such as fertility preserving surgical techniques must be factored in when managing these patients. As the incidence of YOCRC increases, guidance for colonoscopy screening protocols may need revision. This includes evaluating the role of ionising imaging techniques in both diagnosing and follow-up to balance early detection and minimising radiation exposure in this younger patient population.

Low-density lipoprotein receptor-related protein 8 (LRP8) is a crucial regulator of lipid metabolism and is implicated in the development and treatment of various cancers. However, its role in bladder cancer (BCa) remains unknown. We analyzed LRP8 expression in BCa using the TCGA database and clinical samples. We manipulated LRP8 expression in tumor cell lines using siRNA or overexpression plasmid transfection. Cell proliferation, migration, invasion, apoptosis, and drug resistance were assessed through CCK-8, transwell, flow cytometry, and IC50 assays. Additionally, a rescue experiment confirmed the association between LRP8 and lipid metabolism. LRP8 was significantly upregulated in BCa tissues and cells. Knockdown of LRP8 reduced tumor cell proliferation, migration, invasion, and increased apoptosis while enhancing cisplatin sensitivity. Overexpression of LRP8 boosted malignant progression and cisplatin resistance in tumor cells. The expression level of LRP8 is positively linked with the expression of lipid metabolism-related genes, phospholipid accumulation, and triglyceride accumulation. Notably, inhibiting lipid metabolism reversed the malignant progression and cisplatin resistance induced by LRP8 overexpression. LRP8 could promote BCa malignant progression and cisplatin resistance through lipid metabolism regulation.

To develop and validate computed tomography (CT)-based intratumoral and peritumoral radiomics signatures for preoperative prediction of lymph node metastasis (LNM) in patients with ovarian cancer (OC).

Patients with pathological diagnosis of OC were retrospectively included. Intratumoral and peritumoral radiomics features were extracted from contrast-enhanced CT images. Intratumoral and peritumoral radiomics features were extracted from contrast-enhanced CT images. Intratumoral, peritumoral, and combined radiomics signatures were constructed, and their radiomics scores were calculated. Univariate and multivariate logistic regression analyses were performed to identify predictors of clinical outcomes. A radiomics nomogram was developed by incorporating the combined radiomics signature with clinical risk factors. The prediction efficiency of the various models was evaluated using the accuracy value, the area under the receiver-operating characteristic curve (AUC) and decision curve analysis (DCA).

Two hundred and seventy-three patients with OC were enrolled and randomly divided into a training cohort (n=190) and a test cohort (n=83) in a 7:3 ratio. The intratumoral, peritumoral, and combined radiomics signatures were constructed using 18, 11, and 17 radiomics features, respectively. The combined radiomics signature showed the best prediction ability, with accuracy of 0.783 and an AUC of 0.860 (95% confidence interval 0.779-0.941). The DCA results showed that the combined radiomics signature had better clinical application than the clinical model and the radiomics nomogram.

A CT-based combined radiomics signature incorporating intratumoral and peritumoral radiomics features can predict LNM in patients with OC before surgery.

Immunotherapy alone or in combination with chemotherapy or radiotherapy is the frontline treatment for melanoma and lung cancer. However, its role in prostate cancer is usually as a fourth-line treatment. It is usually employed in patients with metastasis, after androgen blockade and chemotherapy. This article reviews the immunosuppressive effects of prostate cancer and possible uses of various types of immunotherapies. It also considers when would be the optimal time to employ this type of therapy.

Pancreatic metastases from renal cell carcinoma (RCC) are usually managed surgically but with significant morbidity. As an alternative, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has shown promising results in treatment of pancreatic neuroendocrine tumors. The aim of our study was to assess technical success, effectiveness, and safety of EUS-RFA in patients with pancreatic metastases of RCC.

This retrospective, observational study included consecutive patients referred for EUS-RFA of pancreatic RCC metastases. EUS-RFA was performed through 18G or 19G dedicated RFA needles. Effectiveness of EUS-RFA treatment was defined by necrosis with no contrast enhancement or lesion disappearance, determined by contrast-enhanced computed tomography (CT) scan, at 2 to 5 months post procedure, 1 year, and at the end of follow-up. Safety was assessed per and post procedure.

Between January 2015 and January 2021, eight patients with 11 lesions were treated and median time from RCC diagnosis to pancreatic metastases RFA was 8.5 years (1-15). Mean lesion size was 13.9 mm (± 3.9). Technical success assessed by immediate post procedure contrast-enhanced CT or Doppler was 100%. At the first CT scan follow-up, complete response was 45.4% and partial response was 27.3%. At 1 year, complete response was 45.4% and partial response was 27.3%. Three patients had multiple EUS-RFAs. Adverse events occurred in 3 patients (mild acute pancreatitis, abdominal pain, and pancreatic fistula with retro-gastric pseudocyst).

Our study demonstrated the feasibility and safety of EUS-RFA for patients with pancreatic metastases of RCC.

Endometrial cancer (EC) is a common gynecological malignancy with increasing incidence, especially in developed nations. Understanding genetic variations, particularly single nucleotide polymorphisms (SNPs), is crucial for uncovering the disease's pathogenesis, progression, and treatment responses. This study explores the global research landscape of SNPs in EC, focusing on field evolution, key contributors, and emerging trends.

A systematic search of the Web of Science Core Collection (WoSCC) retrieved 838 publications on SNPs in EC from 1991 to 2024. Bibliometric indicators, including publication volume, citation counts, and keyword occurrences, were analyzed using VOSviewer, CiteSpace, and the R package "bibliometrix" for visual mapping and trend analysis.

The United States (230 publications) and China (182 publications) were leaders in research output. Harvard University and the National Cancer Institute were prominent contributors. Key themes included "microsatellite instability" (a hallmark of DNA mismatch repair deficiency) and "genome-wide association studies" (GWAS), identifying susceptibility loci like HNF1B and CYP19A1. Recent trends, such as "Mendelian randomization," have enhanced causal inference in risk factor studies. SNP research has advanced risk prediction models and personalized therapeutic strategies, such as hormone therapy tailored to genetic profiles.

SNP research has deepened our understanding of EC's genetic basis, with a growing emphasis on Mendelian randomization and GWAS. These advancements have refined risk prediction and opened new avenues for personalized medicine. Integrating SNP data with environmental and hormonal factors remains crucial for advancing prevention, diagnosis, and treatment strategies in EC.

Dauricine has been shown to possess intriguing anti-cancerous activities against various malignancies. The current study examined the inhibitory effects of dauricine against lung adenocarcinoma with cell lines and animal models. MTT assay was performed in three different lung adenocarcinoma cell lines using a concentration range of dauricine. Colony formation, wound healing, Edu incorporation, and cell cycle analysis were conducted to investigate the impact of dauricine on lung adenocarcinoma cells in vitro. Moreover, flow cytometry was performed to observe the effect of dauricine on cellular ROS levels. The expression of redox regulator Nrf2 and apoptosis-related markers was assessed by Western blot. Importantly, the anti-tumor efficacy of dauricine was studied in vivo with two lung adenocarcinoma animal models, including a subcutaneous cell line-derived syngeneic model and an inducible orthotopic KRASG12D-driven lung adenocarcinoma model. The proliferation and migration of lung adenocarcinoma cells were significantly reduced by dauricine treatment. Flow cytometry analysis revealed that dauricine treatment resulted in cell cycle arrest at G0/G1 phases in A549, H1299, and A427 cells. Intracellular ROS levels were markedly augmented by dauricine treatment. Notably, dauricine led to the downregulation of the master redox regulator Nrf2. Meanwhile, dauricine treatment resulted in decreased Bcl-2 levels but elevated expression of BAX and cleaved Caspase 3. Finally, dauricine demonstrated significant efficacy in restricting tumor progression in both subcutaneous syngeneic and orthotopic lung adenocarcinoma models. Our results corroborate the anti-cancer effects of dauricine against lung adenocarcinoma with in vivo and in vitro analyses. Our findings also provide mechanistic evidence that links the impact of dauricine to cell cycle blockage and ROS-mediated apoptosis.

This study explored the relationship between cognitive function and brain structure in lung cancer (LCs) patients without brain metastases and healthy controls (HCs). A cohort of 75 chemotherapy-naive LCs without brain metastases and 29 age-, sex-, and education-matched HCs underwent cognitive assessments and structural MRI. The MRI focused on cortical thickness, surface area, and volume of subcortical structures. We examined the relationships among these parameters. The volume of twelve subcortical structures was significantly reduced in patients with advanced-stage lung cancer (aLCs) compared to HCs (p < 0.05). In aLCs, cortical thickness decreased in one brain region and surface area in five regions (p < 0.05). Patients with early-stage lung cancer (eLCs) exhibited increased cortical thickness in three regions. When comparing eLCs to aLCs, there was a notable decrease in cortical thickness and surface area (p < 0.05). Visuospatial/executive and delayed memory functions were impaired in aLCs and worsened with disease progression. These impairments correlated positively with the thickness of several cerebral cortices and the surface area and volume of subcortical structures (p < 0.05). Structural brain changes and cognitive dysfunction are evident in aLC patients, independent of metastasis. Since none of the patients received chemotherapy, the observed abnormalities in aLCs, absent in eLCs, are likely attributable to the disease itself rather than chemotherapy effects.

Systemic therapies that have shown a benefit in advanced prostate cancer are being evaluated in earlier disease stages. We sought to determine the prevalence of transcriptomic changes in signatures related to treatment susceptibilities in patients with nonmetastatic prostate cancer.

Patients with nonmetastatic prostate cancer with Decipher genomic classifier and whole-transcriptome profiling data for biopsy specimens from October 2016 to February 2024 were included (n = 140 548). Predefined treatment-related signatures of androgen receptor activity (AR-A), PTEN loss, homologous recombination deficiency (HRD), RB loss, immune activity, and prostate-specific membrane antigen (PSMA; FOLH1) expression, along with Decipher scores and prostate cancer subtypes, were assessed.

The prevalence of low AR-A scores and the basal subtype, which are associated with lower responsiveness to androgen deprivation therapy (ADT), increased with American Joint Committee on Cancer (AJCC) stage and Decipher genomic risk. The prevalence of cancers with a potential response to PI3K inhibitors, according to PTEN loss, and a response to PARP inhibitors, according to HRD status, also increased with AJCC stage and Decipher genomic risk score (all p < 0.001). The prevalence of high PSMA expression was greater in AJCC grade IIC-IIIC disease, so these patients would be potential candidates for PSMA radioligand therapies. More than 60% of patients with AJCC grade IIC-IIIC disease and very high Decipher scores (>0.85) are potential candidates for targeted therapies.

Treatment-related signature scores vary by AJCC stage and Decipher score and may be useful in guiding trials and selecting targeted therapies for nonmetastatic prostate cancer. Higher-stage prostate cancers appear to be more basal and androgen-independent, and thus may be more susceptible to intensified ADT + androgen receptor pathway inhibitors or therapies targeting PARP or PSMA.

Lung cancer is a complex disease with varying subtypes. The genetic architectures and risk factors that are similar or distinct among these subtypes remain unclear. In this work, Genome-wide association studies (GWAS) conducted by the International Lung Cancer Consortium and transdisciplinary Research in Cancer of the Lung were utilized to illustrate the genetic landscapes of different subtypes of lung cancer. GWAS of 942 phenotypes from UK Biobank and 902 phenotypes from FinnGen Biobank were analyzed to identify the genetic risk factors specific or common to each subtype of lung cancer through two sample Mendelian randomization inverse variance weighting method. Multivariable Mendelian randomization was employed to assess the true causals of lung cancer. We found that lung cancer, small cell lung carcinoma, squamous cell lung cancer and lung adenocarcinoma shared similar, yet varied genetic architectures. Genetic risk loci at 15q25 were identified in all types of lung cancer. Yet, genetic risk loci at 5p15 were observed in squamous cell lung cancer and lung adenocarcinoma, but not in small cell lung carcinoma. Out of 942 phenotypes from UK Biobank, smoking, time spent watching television, age first had sexual intercourse, alcohol usually taken with meal and age at first live birth were common risk factors for all types of lung cancer. Moreover, out of 902 traits in FinnGen Biobank, chronic obstructive pulmonary disease (COPD) was positively associated with small cell lung carcinoma, squamous cell lung cancer and lung adenocarcinoma. Angina pectoris and myocardial infarction were negatively associated with lung cancer, squamous cell lung cancer and lung adenocarcinoma. And Alzheimer's disease was negatively associated with lung cancer, small cell lung carcinoma and squamous cell lung cancer. In further weighted median and weighted mode methods, myocardial infarction, angina pectoris and Alzheimer's disease also had genetical associations with lung cancer or its subtypes. Even, considering factors such as smoking, COPD, and other risk factors together, myocardial infarction, angina pectoris and Alzheimer's disease retained the genetical associations with lung cancer and its subtypes. Overall, in a phenome-wide Mendelian randomization analysis, our results have highlighted both similar and distinct risk factors among different subtypes of lung cancer. Additionally, our findings have provided genetic associations linking myocardial infarction, angina pectoris and Alzheimer's disease with lung cancer or its various subtypes.

Melanoma, known for its aggressive behavior and tendency to metastasize to the brain and lungs, is a formidable challenge in oncology. Radiotherapy is a potent treatment for localized solid tumors, effective against both intracranial and extracranial metastases. Yet, some melanoma patients exhibit substantial resistance to radiotherapy, with the underlying mechanisms of this resistance remaining elusive. While radiotherapy can stimulate the infiltration of immune cells, thereby triggering a range of immunostimulatory effects, it can also suppress the tumor microenvironment (TME), limiting its effectiveness. In physiological conditions, cytokines inhibit the activity of immunosuppressive cells through paracrine and autocrine signaling, while also activating immune cells to boost antitumor responses. Here, we found that Interleukin (IL)-21 expression was higher in the mice with good radiotherapy response to melanoma than in the mice with poor radiotherapy response. Interestingly, we also observed the higher infiltration of M2 TAMs and lower CD8+ T cells in the group with poor radiotherapy response. To tackle this issue, we explored the therapeutic potential of a plasmid encoding IL-21, delivered via attenuated Salmonella, in mice bearing melanomas. Our findings revealed that IL-21 administration significantly reduced M2 TAMs infiltration and enhanced CD8+ T cells infiltration and granzyme B (GZMB) expression within melanoma tumors. Most importantly, the combination of IL-21 with radiotherapy led to markedly tumor reduction compared to either treatment alone. This research highlights the potential of IL-21 as a valuable adjunct to radiotherapy in the treatment of melanoma, presenting a promising strategy for enhancing antitumor immune responses and optimizing patient outcomes.

The utility of the immune prognostic index (IPI) for esophageal squamous cell carcinoma (ESCC) has yet to be established after minimally invasive esophagectomy (MIE). The purpose of this study was to investigate the value of IPI in predicting the prognosis and postoperative adjuvant chemotherapy (AC) benefits of ESCC patients.

Between January 2011 and December 2018, 613 ESCC patients underwent MIE at our center and were divided into two groups: low IPI and high IPI.Log-rank tests were used to compare the overall survival (OS) and disease-free survival (DFS) of patients in different groups based on Kaplan-Meier survival analysis. Differences in clinical characteristics between groups were eliminated by propensity score matching (PSM) analysis. To identify independent risk factors influencing OS and DFS, the Cox proportional risk model was used.

In comparison to the high IPI group, the low IPI group had a better 5-year OS and DFS in both the entire and matched cohorts (P < 0.05). IPI was found to be an independent prognostic factor for OS and DFS in a multivariate analysis of the entire cohort and the matched cohort (P < 0.05). In subgroup analyses of most clinicopathological factors, high IPI was associated with a higher risk of death or recurrence in the matched cohorts. When combined with 8th TNM staging, the 5-year OS and DFS of stage II or III patients with low IPI in the AC group were not different from those in the non-AC group (P > 0.05), and AC of stage III patients with high IPI significantly prolonged 5-year OS and DFS (OS: 37.4% vs 26.2%, P = 0.018; DFS: 33.6% vs 19.8%, P = 0.042).

Preoperative IPI is a promising predictor of ESCC after MIE. For stage III ESCC patients with high IPI, AC can significantly reduce the risk of death or recurrence.

In recent years, magnolol (MG), a natural active compound of polyphenolic nature, has garnered significant interest for its anti-cancer effects. Numerous studies conducted on cell lines and animal models have indicated a positive impact of administering drugs or semi-synthesized products derived from MG, including a decreased incidence of various cancers. This review aims to illustrate the underlying cellular and molecular basis of its actions. The article includes in-depth explanations of phytochemistry, semi-synthetic derivatives, bioavailability, pharmacokinetics, preclinical research, anti-tumor mechanisms, human clinical studies, toxicity, side effects, and safety. It also demonstrates that, in contrast to the wealth of synthetic medications, MG is highly effective against bladder, colon, gastric, skin, liver, lung, gallbladder, and prostate cancers. The findings of this review indicate that MG is a promising candidate as an anti-tumor agent, and future research should focus on developing new semi-synthetic derivative compounds with potential anti-tumor properties.

Predicting cancer incidence has long been a challenge for clinicians and researchers. Accurate predictions are essential for health planning to ensure adequate resources for diagnosis, treatment, and rehabilitation. Current prediction methods rely on historical data, assuming persistent patterns of cancer incidence.

In this study, the Google Trends tool was used to obtain the relative search volume index (RSVI) for the topic "cancer" each year from 2017 to 2023 in the United States and worldwide. The proposed model incorporated actual cancer incidence rates and yearly changes in RSVI.

The model was applied to predict the rates of new cancer cases in fifty American states over four consecutive years (2017, 2018, 2019, 2020). The selection of years was restricted with data availability. In most states, the percentage error did not exceed 6%. The high degree of similarity between the actual and predicted cancer incidence rates was notable. Similar results were obtained when predicting cancer incidence rates in the countries studied.

The model has successfully provided accurate short-term predictions of cancer incidence rates across all 50 American states and 54 countries since 2017.