Colorectal cancer (CRC) remains a formidable clinical challenge, many patients exhibit limited responses to conventional chemotherapy and targeted therapies. Although immunotherapy has demonstrated potential, its efficacy is largely restricted to a subset of patients with high microsatellite instability (MSI-H), highlighting the critical need to identify key molecular drivers of immune evasion in CRC. Through comprehensive bioinformatic analysis, we identified the deubiquitinating enzyme JOSD2 as a key player in CRC progression, with elevated expression correlating with poor prognosis in MSI-H patients (HR = 4.79, 95% CI: 3.6-7.96) and dysregulation of multiple immune-related pathways. Mechanistically, we discovered that JOSD2 suppresses cGAS enzymatic activity by removing K27-linked ubiquitination, thereby promoting M2 polarization of macrophages, a process critical for immunosuppression in the tumor microenvironment. Furthermore, using the JOSD2 catalytic inhibitor HY041004, we demonstrated both in vitro and in vivo that the inhibition of JOSD2 activated the cGAS-STING signaling pathway, leading to robust anti-tumor effects in CRC. These findings not only uncover a novel immunomodulatory mechanism in colorectal cancer but also provide a therapeutic rationale for the development of JOSD2-targeted anticancer strategies.

BACKGROUND Hemoperitoneum resulting from a ruptured ovarian cyst is rare but potentially life-threatening, particularly in patients with underlying coagulopathies. Antiphospholipid syndrome (APS) and hereditary antithrombin III (AT III) deficiency represent an exceptionally uncommon concurrent combination. Only 3 prior cases have been documented in the literature regarding thrombotic events; however, none have described acute hemorrhagic complications or their management. CASE REPORT A 28-year-old woman presented with a 24-h history of intractable pelvic pain rated 8/10, accompanied by hypotension, tachycardia, and anemia. She had a history of double-positive APS and hereditary AT III deficiency; she was receiving prophylactic warfarin therapy. Imaging revealed a ruptured hemorrhagic ovarian cyst and moderate hemoperitoneum. Initial management included hemodynamic stabilization, fluid resuscitation, and transfusion of red blood cells and fresh frozen plasma. Anticoagulation was withheld, and a computed tomography-guided pigtail catheter was inserted for pelvic hematoma decompression. After stabilization and confirmation of hemostasis, warfarin therapy was cautiously reinitiated under close international normalized ratio (INR) monitoring. The patient achieved complete clinical recovery and was discharged in stable condition. CONCLUSIONS We present the first documented case of severe hemoperitoneum due to a ruptured ovarian cyst in a patient with concurrent APS and AT III deficiency. This case highlights the complex clinical balance between anticoagulation reversal and thromboprophylaxis in patients with dual hypercoagulable disorders. Future research should aim to develop standardized, evidence-based protocols to guide management and improve outcomes in combined thrombophilic conditions.

Molecular analysis of actionable driver mutations and somatic copy number alterations (sCNAs) in circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) is increasingly being used to guide personalised medicine in patients with cancer. In previous CTC studies, high numbers of CTCs were needed for successful recovery of individual CTCs for molecular analysis at a time when patients typically have very short survival, limiting clinical applicability. Here, by performing longitudinal analyses of ctDNA and CTCs across a broad range of CTC counts, we hypothesized that CTCs could reveal synergistic and additional genomic information to ctDNA at points when therapeutic interventions could be considered in the follow up of patients with metastatic breast cancer (MBC).

Eight patients underwent serial blood sampling. CTCs were captured via CellSearch-DEPArray from 7.5 mL (CellSave tubes), while 15 mL (EDTA tubes) was used for cfDNA extraction. A total of 58 cfDNA samples and 192 CTCs from the 8 patients were compared by shallow whole genome sequencing sWGS and targeted next generation sequencing using custom designed mutation panels (cfDNA; dual barcoding Ion AmpliSeq HD technology (556 hotspots across 24 genes) and CTCs; SingleSeq-compatible AmpliSeq technology across 539 of the 556 (97%) hotspots).

The majority of patient samples showed complementary genomic information in CTCs and ctDNA from the same blood sample. However, genome changes were detected in CTCs from some blood samples that were ctDNA negative despite progression providing actionable information at times when ctDNA analysis was not informative. Across the CTCs and ctDNA, common regions of loss included chromosome 13q14 containing the RB1 gene, detected in 3 of 4 patients receiving CDK4/6 inhibitors and amplification of 17q12 containing the ERBB2 gene in 2 of the 7 patients with HER2 negative metastatic disease, suggesting evolution to HER2 positive disease.

Our study shows that CTCs provide key information that would have been missed by ctDNA monitoring alone and extends CTC and cfDNA genomic profiling to patients with a broad range of CTC counts for blood-based monitoring of HER2 status and other clinically actionable targets for informing treatment decisions in metastatic disease.

Thymomas are typically located in the anterior mediastinum. Primary ectopic intrathyroidal thymoma are exceedingly rare, with only nine cases reported in the English literature. Papillary thyroid carcinoma represents the most common type of thyroid carcinomas, accounting for almost 80% of cases. Herein, we present the first case reported in the literature of primary ectopic intrathyroidal thymomas occurring synchronously with a papillary thyroid carcinoma. We aim to discuss its clinical, morphological, and immunohistochemical features, and highlight the diagnostic challenges posed by this exceptional coexistence.

A 62 year-old North African woman, with no past medical history, presented with a cervical nodule. Cervical ultrasound showed an encapsulated, firm nodule measuring 7 × 5 × 3 cm in the right lobe and a 0.8 cm nodule in the left lobe. Thyroid function and calcium test results were within normal limits. The patient underwent total thyroidectomy. Microscopic examination and immunohitochemical study concluded that there was a primary ectopic intrathyroidal thymoma in the right lobe and a papillary thyroid carcinoma in the left lobe. The postoperative course was straightforward. Given the presence of synchronous papillary thyroid carcinoma, the patient received adjuvant radioactive iodine therapy and remains alive 2 years postoperatively.

Primary ectopic intrathyroidal thymomas are exceedingly rare, with only nine cases previously reported in the literature. Given the nonspecific clinical and radiological presentation, definitive diagnosis relies on pathological examination. Establishing the diagnosis might be challenging given the wide array of potential differential diagnoses. Accurate identification and exclusion of differential diagnoses are essential for appropriate patient management. The coexistence of primary ectopic intrathyroidal thymoma and papillary thyroid carcinoma appears to be incidental.

Several reversal strategies associated with CXCL12, especially the use of CXCR4 antagonists, have been proposed for colorectal cancer (CRC). These strategies have shown some efficacy in clinical trials, but the mechanisms underlying how CXCL12 deficiency contributes to reduced anti-PD-L1 blockade efficacy, a critical barrier to immunotherapy success, remain unclear, highlighting the need for deeper mechanistic exploration and optimized interventions.

In this study, the single-cell transcriptome sequencing analysis, in vitro cell experiments and in vivo animal experiments were integrated to identify CXCL12-related RNA binding proteins (RBPs) with causal links to CRC, define key cell types driving resistance, and validate mechanistic insights.

Twelve CXCL12-related RBPs showed causal relationships with CRC. Machine learning methods and diagnostic analysis identified CPEB3, DDX39B, and SIDT2 as biomarkers of CRC. Monocytes were selected as the key CRC cell type based on their biomarker distribution. Single-cell transcription factor analysis screened out two CRC-related transcription factors: MEIS2 and TCF4. In vitro cell experiments and in vivo animal experiments indicated that CXCL12 silencing promoted the migration and invasion capacities of CRC tumor cells. Notably, CXCL12 overexpression combined with PD-L1 antibodies showed the lowest cell viability and invasion capacity, indicating that CXCL12 enhances rather than inhibits anti-PD-L1 therapeutic efficacy Moreover, CXCL12 was negatively correlated with the proportion and number of myeloid-derived suppressor cells.

Our identification of CPEB3, DDX39B, and SIDT2 as CRC revealed that CXCL12-related CRC biomarkers, combined with mechanistic evidence linking CXCL12 to MDSC regulation and anti-PD-L1 resistance, provides a novel framework for understanding immunotherapy failure in CRC. These findings might aid in establishing clinical CRC treatment strategies guiding the development of CXCL12-targeted combination strategies to overcome anti-PD-L1 resistance and improve CRC immunotherapy outcomes.

The combination of MEK and BRAF inhibitors is effective in melanomas and other tumors with BRAF V600E mutations. MEK inhibitors enhance efficacy and delay the development of resistance to BRAF inhibitors. Recently, MEK inhibitors have demonstrated activity in plexiform neurofibromas in patients with type 1 neurofibromatosis and in histiocytic neoplasms. In the preclinical setting, MEK inhibitors are effective in tumors with RAS or receptor tyrosine kinase mutations. However, after the inhibition of MEK, regulatory feedback determines the rebound activation of ERK, thereby limiting the effect of the MEK blockade. In early clinical trials, MEK inhibitor monotherapy has shown limited efficacy in RAS-mutated tumors, whereas trials combining MEK and RAS inhibitors are still ongoing.

Clinical trials have been selected from clinicaltrials.gov searching for 'MEK inhibitors,' and their results have been searched in PubMed and meeting abstracts. Preclinical studies have been searched in PubMed using the names of the MEK inhibitors. This is a descriptive review.

While MEK inhibitors in combination with BRAF inhibitors obtained one of the first tumor-agnostic FDA approvals for BRAF V600E/K mutated tumors, additional indications for MEK inhibitors alone have been received in very selected diseases for which molecular characterization is crucial.

Brain tumour, either primary or secondary, has produced various widespread or localised symptoms in the patient. They may have a detrimental impact on the quality of a patient's life regardless of subsequent treatment. Palliative care is most effective when it is started early in the disease trajectory. Hence, we conducted this study to assess symptom burden and quality of life (QoL) in brain tumour patients and impact of early palliative care on them.

Prospective analytical study conducted in patients of primary or secondary brain tumour within 4 weeks of their diagnosis. After taking informed consent, all patients were assessed from time of enrolment up to 6 months. Integrated palliative care outcome scale (IPOS) tool was used for symptom burden assessment, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm 20 (EORTC-QLQ-BN-20) tool was used to measure QoL. To know the impact of palliative care, baseline data of these scores were compared with 1^st month, 3^rd month and 6^th month follow-up data.

Total 100 patients enrolled. In IPOS score, statistically significant improvement was noted at subsequent follow-up among physical, emotional and communication scores along with total score. For QoL, significant improvement was noted at subsequent month follow-up in headache, seizures, future uncertainty, bothering due to hair loss and itchy skin among EORTC-QLQ-BN-20.

We conclude that brain tumour patients are suffering from various distressing symptoms. Early involvement of palliative care specialists with neuro-oncology treatment can help in better management of various physical and psycho-social symptoms, which lead to better QoL of patients and their caregivers.

The aim of this study was to evaluate and compare the efficacy, safety, opioid-sparing effect and functional outcomes of computed tomography (CT)-guided versus fluoroscopy-guided celiac plexus neurolysis (CPN) in managing pancreatic cancer pain. The study integrates pain phenotyping using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scale to assess response in neuropathic subtypes.

This was an ambispective observational study conducted at King George's Medical University, encompassing a retrospective cohort (January 2020-December 2022) and a prospective cohort (January 2023-December 2024). Sixty patients with histologically confirmed pancreatic adenocarcinoma and baseline pain scores of ≥7 on the visual analogue scale (VAS) were included. Patients underwent bilateral posterior retrocrural CPN under either CT (n = 30) or fluoroscopic (n = 30) guidance. Neurolysis was achieved using absolute alcohol (6-10 mL) mixed with 2% lignocaine (2-3 mL). Pain scores (VAS and LANSS), opioid use (in morphine equivalents) and functional outcomes (karnofsky performance status [KPS] and short form 36 health survey questionnaire [SF-36]) were recorded at baseline, immediate post-procedure, 1 week, 1 month and 3 months. Complication rates and opioid dose reduction were also evaluated. Statistical analysis was conducted using the Statistical Package for the Social Sciences v26.0 with a significance threshold of P < 0.05.

Both groups were comparable at baseline in terms of age, sex and initial pain scores. The mean VAS decreased from 8.9 ± 1.2 to 5.4 ± 2.1 in the CT group and from 8.8 ± 1.1 to 5.8 ± 2.3 in the fluoroscopy group at 3 months (P = 0.042). LANSS scores showed greater improvement in the CT group (baseline 13.8 ± 1.4-8.2 ± 2.1) compared to the fluoroscopy group (13.6 ± 1.5-9.5 ± 2.3; P = 0.038). Opioid dose reduction of ≥30% was observed in 66.7% (CT) versus 60.0% (fluoro). Functional improvement, assessed by KPS, was greater in the CT group (+15 points) than in the fluoroscopy group (+12 points). Complications were significantly lower in the CT group (20%) compared to the fluoroscopy group (46.7%, P = 0.019), with diarrhoea and hypotension being the most common.

Both CT and fluoroscopy-guided CPN provide effective pain relief in pancreatic cancer. However, CT-guided CPN is associated with significantly greater pain reduction, especially in patients with neuropathic pain features, lower complication rates and better functional outcomes. Pain phenotyping using LANSS enhances procedural decision-making and supports a personalised approach to palliative care in pancreatic malignancy.

Osteosarcoma and other solid tumor therapies remain urgent clinical challenges. Currently, treatment mainly relies on surgical resection. However, surgery often requires extensive removal of bone and surrounding tissues, which can easily lead to impaired limb function, affect patients' immune and metabolic functions, and increase the risk of recurrence. Smart nanomedicine offers new hope for the treatment of solid tumors. Nanoparticles can enable targeted drug delivery and personalized treatment, reduce damage to normal tissues, and help prevent dysfunction and disability. Postoperative adjuvant nanomedicines can help eliminate residual tumor cells, lower the recurrence rate, control distant metastasis, and improve survival rates. Additionally, nanoparticle-based immunotherapy has shown promising prospects. By integrating artificial intelligence and big data platforms, the development of smart nanomedicine systems can become more efficient, reliable, and tailored to the specific needs of osteosarcoma therapy. However, there are still biosafety, ethical, and regulatory challenges in clinical translation. In the future, it is necessary to further optimize the targeting and biocompatibility of nanocarriers, strengthen research on tumor metabolism, and improve regulatory systems to promote the clinical application and commercial development of multifunctional nanoparticles.

This article reports a rare case of a patient with POEMS syndrome who developed secondary myelodysplastic syndrome (MDS) two years after undergoing autologous stem cell transplantation (ASCT). The patient was initially misdiagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP) due to symptoms of limb numbness and weakness. Two years later, the diagnosis was corrected to POEMS syndrome. After induction therapy with the lenalidomide-dexamethasone (RD) regimen, ASCT is performed and partial remission is achieved. And lenalidomide was used for maintenance therapy. Over a year later, he was infected with SARS-CoV-2 and subsequently developed pancytopenia. Bone marrow routine revealed increased myeloblasts with multilineage dysplasia, and next-generation sequencing (NGS) found a TP53 mutation, leading to the diagnosis of secondary MDS. The pathogenesis of secondary MDS in POEMS syndrome is discussed from three aspects: cytotoxic therapy, genetic predisposition, and SARS-CoV-2 infection. This case underscores the importance of prolonged surveillance for secondary myeloid neoplasms (sMN) in POEMS patients and suggests that early genomic profiling and individualized treatment may improve outcomes.