Pilonidal disease (PD) is a common inflammatory disease of the gluteal region with an incidence of 26/100000 and usually occurs in young males (15-30 years old). The etiology of pilonidal disease is unclear, but literature describes a wide range of factors such as keratin plugs, foreign substance reaction related to hairs, as well as dermatopathy and debris in hair follicles in the natal cleft. PD and also its classic treatment can cause discomfort and very much deteriorate the patient's quality of life. There are many possibilities (conservative or surgical) in the treatment of pilonidal disease, but there is no gold standard. In the acute phase (abscess), surgical incision with pus evacuation and antibiotic therapy is enough. In the chronic phase, there are many possibilities like phenol treatment, surgical excision with lay open and secondary wound healing. There are many reconstructive techniques such as Karydakis, V-Y flap or Limberg flap. A recently minimally invasive technique such as endoscopic surgical procedure or filling pilonidal tract with fibrin glue or phenol have been introduced. We present our experience with laser treatment (Biolitec, Germany) of pilonidal sinus disease.

Terminally ill cancer patients often experience pain and delirium. However, opioids administered for pain management may exacerbate patients' delirium.

To explore the real-world symptom trajectory associated with pharmacological interventions, including opioids and antipsychotics, in patients with cancer pain and terminal delirium.

A secondary analysis of a multicenter prospective observational study.

Adult patients admitted to inpatient hospice or palliative care units in Japan. Participants were eligible if they had cancer pain (Integrated Palliative care Outcome Scale: IPOS ≥2) and delirium at the time that their Palliative Performance Scale had declined to ≤20 (day 1, immediately before death).

Pharmacological strategies, pain levels (using the IPOS), and delirium symptoms (using the Memorial Delirium Assessment Scale, item-9).

Among a total of 1896 patients, 1396 were assessed for eligibility on day 1, and 137 met the inclusion criteria for analysis. A total of 86 (63%) patients had agitated delirium (hyperactive or mixed) with a median survival time of three days. Regarding pharmacological strategies, 32 (23%) received opioid initiation/dose escalation and 94 (69%) received regular administration of antipsychotics. These figures also included 25 (18%) patients who received both opioid initiation/dose escalation and antipsychotics. Approximately 55% of all patients had persistent cancer pain (IPOS for pain ≥2) on day 2. Among those with agitated delirium, 79% continued to exhibit agitation symptoms on day 2.

Despite specialized palliative care, the combined distress of cancer pain and delirium in the last days of life remains complex and refractory.

Recurrent/metastatic head and neck squamous cell carcinoma ((R/M) HNSCC) represents one of the most aggressive and immunosuppressive cancers. Despite the introduction of immune checkpoint inhibitors (ICIs), only a limited number of patients obtain long-term benefits. In (R/M) HNSCC patients, the antitumor immune response is defective, conferring resistance and promoting tumor progression. Therefore, the identification of novel biomarkers for superior clinical outcomes and easily accessible in standard clinical settings is still an unmet clinical need.

Blood liquid biopsies obtained from (R/M) HNSCC patients undergoing pembrolizumab therapy (monotherapy or in combination with chemotherapy) were analyzed by flow cytometry to evaluate the levels of circulating immunosuppressive regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs), at baseline and during therapy. Correlations between these immunosuppressive immune cell subsets and clinical parameters (clinical response rate, progression-free survival (PFS), overall survival (OS) and performance status (PS)) were performed.

Univariate analysis showed that before therapy, higher circulating levels of both CD137⁺Tregs and LOX-1⁺PMN-MDSCs, identified patients with significantly worse survival. Furthermore, CD137⁺Tregs resulted also positively correlated with worse PS, while high levels of LOX-1⁺PMN-MDSCs negatively affected response to pembrolizumab, with a significant increase in non-responsive patients during therapy. Interestingly, both CD137⁺Tregs as well as LOX-1⁺PMN-MDSCs exerted a higher immunosuppression on T cell proliferation than CD137^-Tregs and LOX-1⁻PMN-MDSCs, respectively. Multivariate analysis revealed that the circulating LOX-1⁺PMN-MDSC subset resulted as an independent prognostic factor for survival by multivariate analysis, as confirmed in an independent validation cohort.

The levels of blood circulating LOX-1⁺PMN-MDSCs may be proposed as non-invasive biomarkers to predict clinical outcomes of (R/M) HNSCC patients developing resistance to immunotherapy, improving patient selection and suggesting novel personalized therapies.

Esophageal cancer (EC) is a common malignancy with poor prognosis. Telomeres, composed of repetitive DNA sequences and shelterin complexes, play important roles in tumor biology. However, the prognostic value of telomere-related genes (TRGs) in EC remains unclear.

TRGs were obtained from TelNet, and transcriptomic and clinical data were collected from The Cancer Genome Atlas (TCGA). Prognostic TRGs were identified using multivariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest (RF), and Support Vector Machine (SVM) algorithms to construct a risk model. Model performance was evaluated by Kaplan-Meier(K-M) and Receiver Operating Characteristic (ROC) analyses, and a nomogram integrating clinical variables was developed. Somatic mutations, immune infiltration, immunotherapy response, and drug sensitivity were compared between high- and low-risk groups. In addition, functional assays were performed to verify the biological role of the key gene PTGES3.

Six TRGs significantly associated with prognosis were identified to establish a risk model. High-risk patients had worse survival, higher TP53 and TTN mutation rates, altered immune infiltration, poorer predicted immunotherapy response, and distinct drug sensitivity profiles. Knockdown of PTGES3 significantly suppressed EC cell migration, invasion, and clonogenic ability, supporting its oncogenic role.

A TRGs-based prognostic model effectively predicts survival in EC and reveals associations with somatic mutations, immune infiltration, and drug sensitivity. Functional validation of PTGES3 further supports its potential as a therapeutic target.

Tumorigenesis is closely related to defects in DNA damage response (DDR), which plays an important role in maintaining genomic integrity. The DDR process includes DNA damage recognition, cell cycle checkpoint pathway activation, and DNA damage repair. On the one hand, defects in DDR increase the instability of the cellular genome, which ultimately leads to tumorigenesis. On the other hand, tumor therapy can take advantage of DDR defects to induce apoptosis by causing damage to tumor cells, thus achieving therapeutic goals. Tumor immunotherapy is an emerging method of tumor treatment that attacks and kills cancer cells by inhibiting negative regulatory factors, enhancing the ability of immune cells to recognize antigens on the surface of tumor cells and activating the patient's own immune system. Recent research evidence suggests that DDR inhibition enhances antitumor immune responses and acts in synergy with immunotherapy. This review describes the different categories of DNA damage, their corresponding DNA damage repair pathways, the antitumor mechanisms of action targeting DDR inhibition, and the prominent contributions of these mechanisms to the immunotherapeutic response. By exploring recent advances in the interactions between targeted DDR and immunotherapy, this review provides novel therapeutic insights into the treatment of DNA damage-associated cancers as well as the development of combination immunotherapy.

Accumulating evidences have indicated that PDZ and LIM domain 2 (PDLIM2) served as a critical tumor suppressor in hepatocellular carcinoma (HCC). However, the precise molecular mechanisms underlying its diminished protein expression in HCC pathogenesis remain poorly characterized. In this study, we revealed that PDLIM2 downregulation enhanced malignant proliferation of HCC cells. Mechanistically, PDLIM2 interacted with tripartite motif-containing protein 27 (TRIM27), facilitating its K27-linked polyubiquitination-mediated proteasomal degradation. This posttranslational modification consequently attenuated STAT3 signaling activation. Furthermore, we elucidated that pre-B-cell leukemia transcription factor-interacting protein 1 (PBXIP1) overexpression in HCC enhanced the polyubiquitination of PDLIM2 through the ubiquitin‒proteasome system, which was responsible for PDLIM2 protein destabilization in HCC. Collectively, our findings reveal that the PBXIP1-mediated posttranslational regulation of PDLIM2 contributes to its tumor-suppressive effects via the modulation of the TRIM27/STAT3 oncogenic axis during HCC progression.

Immunotherapy has achieved remarkable progress in treating cancers that evade immune surveillance. Among the components of the tumor microenvironment, macrophages play important roles in maintaining homeostasis, preventing pathogen invasion, engulfing and promoting the adaptive immune response. It is acknowledged that blocking the CD24-Siglec-10 interaction significantly enhances the macrophage phagocytosis ability. In this study, we identified CD24 as an over-expressed molecule in ovarian and breast cancer using data from the GEO database and clinical samples. We then developed genetically programmable extracellular vesicles displaying CD24 single-chain variable fragment (CD24 scFv-EVs) and evaluated their ability to restore macrophage phagocytic activity and eliminate CD24-overexpressing cancer cells. Our findings demonstrate that CD24 scFv-EVs effectively block CD24 on ovarian cancer cells as well as breast cancer cells, thereby inhibiting the CD24-Siglec-10 pathway and enhancing macrophage-mediated clearance of cancer cells. Furthermore, CD24 scFv-EVs promote the polarization of tumor-infiltrated macrophages toward an M1-like phenotype. These results highlight CD24 blockade as a novel therapeutic strategy to target ovarian and breast cancer cells and enhance macrophage-driven tumor cell clearance.

Asporin (ASPN) was shown to be highly expressed in gastric cancer. The purpose of this study was to investigate the relationship between ASPN expression and invasion, migration, macrophage M2 polarization and prognosis of gastric cancer.

ASPN expression in tumor and normal tissues was analyzed using TIMER, GEPIA, and HPA databases. Its clinical prognostic value was evaluated using Kaplan-Meier plotter and GEPIA databases. The association of ASPN with clinicopathological parameters was explored using the cBioPortal datasets. The TIMER and Aclbi databases were used to assess the relationship between ASPN and tumor immune infiltration, and TIMER and GEPIA were used to analyze correlations with immune infiltrate gene markers. Immunohistochemistry detected ASPN protein in 436 gastric cancer tissues and analyzed its correlation with clinicopathological parameters and prognosis. Transwell assays were used to assess ASPN's impact of ASPNs on the migration and invasion of HGC27 and AGS gastric cancer cells. GSEA was used to investigate cellular mechanisms associated with ASPN expression. The possible regulatory pathways of ASPN that promote M2 macrophage polarization were analyzed using RNA-seq.

ASPN expression was elevated in 51.8% of gastric cancer cases and was correlated with poor survival rates, higher tumor stage, and histologic grade. It is significantly linked to the presence of various immune cells and markers, particularly monocytes/macrophages and regulatory T (Treg) cells. High ASPN expression is associated with multiple cancer-related pathways. ASPN upregulation is linked to the Lauren classification, differentiation, invasion depth, lymph node and distant metastasis, and TNM staging. Patients with low ASPN expression had a 5-year survival rate of 53.8% compared to 28.8% for those with high expression. Overexpression of ASPN upregulates migration and invasion of AGS and HGC-27 cells. TIMER database analysis indicated that ASPN was positively correlated with M2 macrophage markers (such as CD163) but not with M1 markers. ASPN upregulation in gastric cancer is closely associated with M2 macrophage polarization and a poor prognosis. KEGG pathway analysis revealed that increased ASPN levels are significantly associated with the neutrophil extracellular trap (NETs) pathway.

ASPN is highly expressed in gastric cancer and is associated with poor prognosis by promoting invasion and migration and inducing macrophage M2 polarization.

During hyperthermic intraperitoneal chemotherapy (HIPEC), high intra-abdominal pressure (IAP) increases the penetration depth of chemotherapeutic agents. Cisplatin is one of the most commonly used chemotherapeutic agents during HIPEC, and nephrotoxicity is the most common adverse effect. In this study, we aimed to evaluate the relationship between IAP increase, cisplatin levels in the blood, and early complications.

During HIPEC, IAP was measured using a catheter placed in the intra-abdominal area. Those with IAP < 18 mmHg were classified into the low-pressure group, while those with IAP between 18 and 22 mmHg were classified into the high-pressure group. At the end of surgery, cisplatin levels were measured in the blood collected at 24 h and in urine collected during the first 24 h. Surgical data, postoperative blood levels, urine output, and 30-day morbidity and mortality outcomes were evaluated.

A total of 36 patients were included in the study: 17 in the low-pressure group and 19 in the high-pressure group. Although cisplatin levels in blood samples taken at 0 and 24 h postoperatively were higher in the high-pressure group, this difference was not statistically significant. There were no differences between the groups in terms of postoperative urea and creatinine levels or the incidence of postoperative complications.

Our study demonstrated that different IAP during HIPEC do not affect the systemic circulation of cisplatin or short-term systemic complications.

Lung cancer is one of the most prevalent malignant tumors with high morbidity and mortality rates worldwide. Extensive multi-omics analyses have revealed significant intratumoral heterogeneity even within the same histopathological subtype. However, a database that systematically integrates multi-omics data for lung cancer research has long been lacking. Here, we developed LOSTdb, a molecular subtype annotation system for lung cancer that integrates multi-omics data and metadata. LOSTdb comprises 295 multi-omics datasets, including bulk RNA-seq, genomic, proteomic, methylation, and scRNA-seq data, with over 10,000 manually curated metadata entries. This resource encompasses high-quality clinical specimens, mouse models, and cell lines, totaling 34,393 samples and more than 1.2 million single cells. Each omics sample was annotated with both literature-based classical subtypes and NMF-derived meta-program (MP) subtypes. The platform supports cross-searching of omics and metadata at the gene and dataset levels, offers multiple visualization and analysis methods, and includes five tool modules, enabling functions such as integrated analysis, significance analysis between metadata as well as between genes and metadata, and target prediction for lung cancer molecular subtypes, serving as an essential tool for lung cancer precision medicine. LOSTdb is a user-friendly interactive database freely accessible at http://lostdbcancer.com:8080 .