Polycystic ovarian syndrome (PCOS) has bidirectional effects on the skeleton due to hormonal dysfunction and insulin resistance (IR).

We examined bone mineral density (BMD) and its relationship with IR using the homeostasis model of assessment (HOMA) in patients with PCOS and matched controls.

In this case-control observational study, we included 74 patients newly diagnosed with PCOS and a similar number of age-and weight-matched healthy women as controls. Haematological, biochemical and hormonal parameters were measured in a fasting blood sample during the follicular phase, and the BMD Z score was calculated using dual energy X-ray absorptiometry. The results were analysed using relevant statistical methods, and P < 0.05 was considered significant.

The study participants ( n = 148) had a mean age of 23.6 ± 3.7 years and a body mass index (BMI) of 25.2 ± 3.2 kg/m 2 . Among the PCOS patients, 25 (34%) had a normal BMI and 49 (66%) were obese. The BMD at the femoral neck ( P = 0.4313) and lumbar spine ( P = 0.1410) was comparable between the PCOS and control groups. Correlation analysis showed a positive correlation of BMD with testosterone and 17-hydroxy progesterone (17OHP) ( P < 0.001). None of the BMD parameters correlated with HOMA in either group.

BMD at the lumbar spine and femoral neck was similar between patients with PCOS and controls. Further studies with a larger sample size, longer follow-up periods and fracture data are needed to confirm our findings.

We show continuous tumor exposure results in a loss of chimeric antigen receptor (CAR) T cell (CART) endocytic activity due to downregulation of Rab5. Loss of endocytic activity exacerbates the effects of trogocytosis, the bidirectional transfer of tumor target antigens and CARs between malignant cells and CARTs, resulting in CART dysfunction and fratricide. Constitutive expression of Rab5 within the CARTs reduced fratricide by reducing the amount of trogocytosed antigens on the cell surface, while simultaneously enhancing CAR availability through dissociation of CAR from target, recycling unbound CAR back to the plasma membrane, and limiting CAR capture by tumor cells. Rab5-expressing CARTs exhibited superior antitumor activity in both BCMA-CARTs isolated from the bone marrow of treated patients and mesothelin-specific CARTs in a solid tumor model. These studies uncover an unexpected relationship between endocytosis and CART function and suggest that pairing Rab5 with CAR expression could improve the clinical efficacy of CART therapy.

Esophageal squamous cell carcinoma (ESCC) is characterized by intrinsic radioresistance, primarily mediated by hyperactivation of DNA damage response (DDR) pathways. This repair capacity significantly diminishes radiotherapy efficacy, contributing to poor patient outcomes. Targeting DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a master regulator of non-homologous end joining (NHEJ), represents a promising strategy to overcome radioresistance. Immunohistochemistry (IHC) was performed on paired biopsy specimens from esophageal squamous cell carcinoma (ESCC) patients (n = 20) collected before neoadjuvant radiotherapy and after surgical resection. In vitro, ESCC cell lines (TE13 and Eca9706) were co-treated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) inhibitors (AZD7648 or NU7741) or PRKDC-targeting siRNA plus irradiation. Subsequent functional assays were conducted to assess cell viability, apoptosis, cell cycle distribution, and underlying molecular mechanisms. In vivo, the combined efficacy of AZD7648 and irradiation was evaluated in xenograft tumor models. Phosphorylated DNA-PKcs (Ser2056) in ESCC tissues was significantly elevated following irradiation. Inhibition of DNA-PKcs markedly enhanced radiosensitivity in both ESCC cell lines and xenograft models, correlating with prolonged G2/M arrest and increased apoptosis. Mechanistically, the combined therapy activated the ATM (Ser1981)-Chk2 (Thr68) axis and concurrently enhanced phosphorylation of Chk1 at Ser345, reinforcing G2/M arrest through Wee1 kinase-mediated inhibitory phosphorylation of CDC2 at Tyr15. Consequently, irreparable DNA double-strand breaks (DSBs) accumulated, triggering Caspase-3-dependent cleavage of PARP and execution of the intrinsic apoptosis pathway. Our study reveals a novel mechanism by which DNA-PKcs inhibition augments radiosensitivity in ESCC. Targeting DNA-PKcs could represent a promising strategy to improve the efficacy of radiotherapy in ESCC, offering a potential therapeutic approach to overcome radioresistance.

Determining microsatellite instability (MSI) status in colon cancer is crucial for selecting treatment strategies in advanced stages. Thus, accurately identifying MSI status before treatment is essential.

This study aims to evaluate the utility of nomogram model that integrates clinicopathological indicators and pre-treatment CT-based radiomics features for predicting DNA mismatch repair deficiency (dMMR) /microsatellite instability (MSI) status in colon cancer prior to treatment.

A total of 201 colon cancer patients who had undergone preoperative contrast-enhanced CT scans were categorized into the dMMR/MSI group or the proficient Mismatch Repair (pMMR)/Microsatellite Stable (MSS) group based on surgical pathology results. Multivariate logistic regression was applied to identify independent clinical predictors. The least absolute shrinkage and selection operator (LASSO) regression was applied for dimensionality reduction of radiomics features. Clinical, radiomics, and nomogram models were established through logistic regression analysis based on the risk clinicopathological predictors and radiomics features.

Multivariate logistic regression identified patient age, pericentric lymph node metastasis, and CA72-4 levels as significant (P < 0.05). Four radiomic features were selected to construct the radiomics model. In the training set, the AUC values for the clinical model, Rad score, and combined model were 0.86, 0.89, and 0.94, respectively, and in the validation set, 0.81, 0.89, and 0.91, respectively. The Delong test showed the nomogram model outperformed both the clinical model and Rad score (P < 0.05). The calibration curve confirmed good consistency between predicted and actual outcomes for dMMR/MSI colon cancer using the combined model.

The nomogram model, which combines clinicopathological features with pre-treatment CT-based radiomics features, demonstrates greater predictive accuracy for dMMR/MSI colon cancer than the standalone clinical and radiomics models.

Triple-negative breast cancer (TNBC) presents a poorer prognosis than other breast cancer subtypes, attributed to its aggressive nature and the lack of specific therapeutic interventions. TNBC has high recurrence rates and limited survival despite current therapies, emphasizing the critical need for improved treatment options. TNBC exhibits increased levels of LRP6 expression, which is linked to tumor-related features such as growth, metastasis, poor prognosis, resistance to chemotherapy, and invasion. Therefore, LRP6 offers a promising option for therapeutic intervention in breast cancer.

This research aims to use in silico and bioinformatics techniques to develop an mRNA vaccine that specifically targets the LRP6 antigen.

The final vaccine construct comprised 431 amino acids, with a molecular weight of 47.5 kDa, theoretical pI of 5.11, and an instability index of 38.3 indicating stability. Population coverage analysis showed broad global coverage of 99.04%. Molecular docking revealed strong binding affinities to immune receptors, including HLA-A0201 (-812.0), HLA-A0301 (-707.1), HLA-DRB1*0101 (-955.7), and TLR9 (-1339.5). Immune simulation predicted high titers of IgG1 antibodies, sustained memory B cell populations (> 200 by Day 365), elevated CD4+ T cells (> 3000), and robust IFN-γ responses. Codon optimization yielded a high CAI value of 0.94 and GC content of 58.37%, supporting efficient expression in human systems.

Collectively, these results suggest that the designed LRP6-targeted mRNA vaccine could induce durable humoral and cellular immunity against TNBC and warrants further experimental validation.

Accurate size estimation of large (≥ 20 mm) colorectal laterally spreading tumors (LSTs) is essential for procedural planning, risk stratification, and predicting technical difficulty. Yet, the reliability of visual LST size assessment among endoscopists has not been systematically evaluated.

46 LSTs were recorded during colonoscopy. Twenty-four international expert endoscopists independently reviewed de-identified videos and provided visual estimates for (1) maximal diameter, (2) oral-anal axis, (3) left-right axis, and (4) percentage of colonic circumference involved. Each lesion was assessed twice in randomized order. Fleiss's kappa, Krippendorff's alpha, and intraclass correlation coefficients (ICC) were used to evaluate inter- and intra-rater agreement.

A total of 1104 measurements were collected. Inter-endoscopist kappa agreement for maximal diameter was poor (κ = 0.16), with similarly poor agreement for the oral-anal (κ = 0.15) and left-right axes (κ = 0.14). The percentage of circumferential involvement demonstrated moderate reproducibility (ICC 0.74 and 0.70 across rounds). Subgroup analyses showed consistently poor agreement for larger lesions for diameter-based methods, whereas circumferential percentage estimation ranged from poor to good depending on LST size and morphology. Intra-endoscopist agreement for diameter- and axis-based approaches showed wide variability (κ range 0.01-0.67), while circumferential estimates achieved good to excellent agreement for most endoscopists.

Visual estimation of large colorectal LST size is highly variable among expert endoscopists. Maximal diameter and axial lengths demonstrate poor inter- and intra-observer reliability. Circumferential extent is the most reproducible descriptor and may be the preferred approach for reporting LST size in clinical practice and research.

Colorectal cancer is one of the most common types of cancer with hereditary background. Due to the progress in DNA sequencing techniques, the number of identified cancers predisposing gene mutations is rising constantly. For some morphologically defined cancer predispositions like serrated polyposis, however, a genetic background is rarely identified. Even if this would exclude a hereditary predisposition, the elevated cancer risk remains, emphasizing the importance of histopathologic diagnoses.Hereditary colorectal cancer can be categorized into polypous and non-polypous predispositions. While the former elevate cancer risk by increasing the number of cancer precursors, the latter elevate cancer risk by increasing the likelihood of malignant transformation. It is the pathologist's responsibility to use morphologic criteria in combination with clinical data in order to raise suspicion of hereditary tumorigenesis and recommend genetic counselling. This article summarizes the current state of knowledge on hereditary colorectal cancer.The new German S3 guideline for colorectal cancer demands testing of all newly diagnosed colorectal cancers for Lynch syndrome association. Owing to this change in the guideline, this article will focus on diagnostic challenges of the DNA mismatch repair function.

Pharmacologic targeting of murine double minute 2 (MDM2) represents one of the most compelling strategies for therapeutic reactivation of wild-type p53 in hematologic malignancies. The MDM2-p53 autoregulatory loop is a central regulator of cellular stress responses, and in myeloid neoplasms-including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN)-p53 is frequently retained but functionally suppressed through MDM2 overexpression and oncogenic signaling, notably via JAK-STAT activation. Over the past decade, successive generations of MDM2 inhibitors have translated structural and mechanistic insights into clinical investigation, yielding critical lessons regarding dosing paradigms, hematologic toxicity, biomarker-driven patient selection, and mechanisms of resistance, including TP53-mutant clonal selection. While early phase III trials in AML were negative, recent studies in myelofibrosis demonstrate clinically meaningful spleen, symptom, and molecular responses, supporting disease-modifying potential in TP53-wild-type settings. Adaptive platform designs and rational combinations with JAK inhibitors, BCL-2 antagonists, and interferons have further refined therapeutic strategies. Emerging MDM2 degraders and next-generation agents aim to overcome feedback limitations and improve therapeutic index. This review integrates mechanistic foundations, clinical development, resistance biology, and future directions, highlighting how decades of basic science have reshaped p53 reactivation into a precision therapeutic paradigm in myeloid disease.

Spiritual and religious concerns are an integral yet often overlooked component of distress in cancer care. The National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) includes a "spiritual/religious concerns" item on its Problem List, but little is known about how this item is used or how it informs clinical care.

This targeted review examined how spiritual distress is identified and addressed using the DT in oncology settings. A PubMed search yielded 44 articles; six met inclusion criteria. Most studies were cross-sectional, conducted outside the United States, and varied widely in design, populations, and measurement tools.

Findings suggest that spiritual/religious concerns are endorsed by a meaningful subset of patients-especially during active treatment or at critical points such as diagnosis or recurrence-and often coincide with high distress scores. However, prevalence rates varied significantly (5%-60%), and few studies evaluated whether positive screens led to referrals or meaningful spiritual support. Only two studies used validated measures of spiritual well-being alongside the DT, and some findings-such as unexpectedly strong correlations between spiritual well-being and anxiety/depression-warrant further investigation.

Despite its inclusion in a widely used screening tool, the spiritual/religious concerns item remains underutilized and poorly understood. This review identifies major gaps in understanding when and how spiritual concerns arise, what influences their reporting, and how needs are addressed in practice. In the United States, where the DT is routinely collected, these gaps present a clear opportunity for targeted research and implementation efforts to improve holistic, values-aligned cancer care through better spiritual support integration.

Carbon-11 methionine positron emission tomography (¹¹C-methionine PET; Met-PET) is widely used in neuro-oncology for preoperative tumor characterization, differentiating recurrence from radiation necrosis, and determining stereotactic biopsy targets. Although its role in gliomas has been well established, evidence supporting its value in germ cell tumors, particularly teratomas, remains limited. An 18-year-old man presented with diplopia, photophobia, and a headache. Magnetic resonance imaging (MRI) revealed a pineal tumor. Serum AFP was 31.5 pg/mL, serum β-HCG < 1.0 mIU/mL, and CSF PLAP 23.6 pg/mL. After three courses of CARE chemotherapy and local radiotherapy, gross total resection was performed at another hospital. He subsequently developed hydrocephalus and underwent endoscopic third ventriculostomy at our institution. MRI and Met-PET showed no residual lesions. Additional ICE chemotherapy resulted in the normalization of tumor markers. However, MRI performed 4 months after resection demonstrated a new enhancing lesion in the right posterior thalamus, and Met-PET revealed new uptake (SUVmax, 2.64; TNR, 2.08), suggesting recurrence. A second craniotomy achieved gross total resection of the whitish, elastic, well-demarcated lesion. Histopathology showed mainly granulomas with inflammatory changes, but no viable tumor cells. The postoperative course was uneventful, and no recurrence has been observed for 3 years. This case suggests that in germ cell tumors, particularly teratomas, Met-PET findings may be misleading and do not necessarily indicate viable tumor tissue. Further studies are required to clarify the clinical significance of Met-PET for teratomas.