To investigate the expression of KRT80 in non-small cell lung cancer (NSCLC) patients and its relationship with clinicopathological factors, prognosis, as well as the differences in KRT80 expression between Xuanwei area and Non-xuanwei area, lung adenocarcinoma and lung squamous cell carcinoma. Based on 178 clinical cases, immunohistochemical methods combined with public databases were used to examine the expression of KRT80 in NSCLC patients and analyze its correlation with various clinicopathological factors and prognosis. The study confirmed the up-regulation of KRT80 expression in NSCLC cancer tissues. Significant regional specific and histological subtype differences in KRT80 expression were revealed. Although the expression level of KRT80 has no direct significant correlation with the prognosis of NSCLC patients, it has a good ability to distinguish cancerous tissue from paracancer tissue. KRT80 can be used as a diagnostic biomarker for NSCLC patients, but its specific mechanism and clinical application value still need to be further explored.

Early papillary gastric adenocarcinoma (EPGA), a well-differentiated gastric adenocarcinoma, is characterized by higher malignancy and worse prognosis compared to other differentiated gastric adenocarcinomas. Therefore, there is a critical need to elucidate its clinicopathological features and mucin expression for accurate diagnosis. The data of 116 cases of EPGA and 116 cases of early well-moderately differentiated tubular gastric adenocarcinoma (ETGA) diagnosed via pathological examination following radical gastrectomy from January 2016 to December 2023 at the Second Hospital of Shandong University were collected. Multivariable logistic regression was used to conduct a comparative analysis of the two groups of variables. The features of histological grading and immunophenotype, particularly mucin expression, were specifically analyzed. The receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy of potential biomarkers in distinguishing EPGA from ETGA. The features of histological grading and MUC5AC expression in EPGA were specifically analyzed. Additionally, the risk factors of LVI in early gastric cancer (EGC) were assessed. EPGA exhibited significantly larger size (P < 0.001), higher frequencies of elevated appearance (P = 0.001), ulcer formation (P = 0.010) and lymphovascular invasion (LVI, P = 0.050) compared to ETGA. The expression of mismatch repair-deficient (P = 0.005) and MUC5AC (P < 0.001) were significantly elevated in EPGA compared to ETGA. Compared to ETGA, high-grade EPGA exhibited a greater incidence of ulcer formation (P < 0.001), submucosal invasion (P = 0.007), LVI (P = 0.010) and microsatellite instability-high (MSI-H, P < 0.001), whereas low-grade EPGA demonstrated clinicopathological characteristics similar to ETGA. MUC5AC expression was associated with LVI (P = 0.034) and MUC6 (P = 0.017) in EPGA. Moreover, high expression of MUC5AC showed good diagnostic efficiency in distinguishing EPGA (AUC = 0.724, 95% CI = 0.66-0.79). When EGC infiltrated the submucosa (OR = 25.227, 95% CI = 4.017-158.432; P < 0.001) or exhibited MSI-H phenotypes (OR = 10.708, 95% CI = 1.478-77.565; P = 0.019), LVI was more likely to occur. The retrospective study elucidates the clinicopathological features and mucin expression profiles of EPGA. The complex architecture and pronounced nuclear atypia observed in high-grade EPGA are indicative of higher malignancy. Moreover, the high expression of MUC5AC suggests a strong likelihood of EPGA, which may aid in its differentiation. In addition, MSI correlates with the presence of LVI in EGC.

The aim of this study was to investigate the mechanisms of acquired resistance to anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC), with a focus on the role of KRAS secondary mutations. We sought to evaluate how these mutations contribute to resistance in patients treated with chemotherapy alone or in combination with cetuximab, and to explore the impact of treatment duration and disease progression on mutation rates. We retrospectively collected data from 50 mCRC patients with wild-type KRAS who received either chemotherapy alone or chemotherapy combined with anti-EGFR therapy (cetuximab). Following treatment, tumor samples were recollected through surgery, biopsy, or colonoscopy. The secondary mutation status of KRAS, NRAS, and BRAF was determined via an amplification refractory mutation system. Based on the nature of the chemotherapy regimen and the presence or absence of tumor progression at the time of the second KRAS mutation analysis, patients were stratified into three groups: Group A (adjuvant chemotherapy and recurrence), Group B (first-line chemotherapy without progression), and Group C (first-line chemotherapy with progression). Secondary KRAS mutations were assessed in relation to therapeutic regimens and progression profiles to investigate the mechanisms of acquired resistance to anti-EGFR therapy. The overall rate of secondary KRAS mutations was 6.0% (3/50). These mutations were not observed in patients treated with chemotherapy alone (0/24), but occurred in 11.5% (3/26) of patients receiving chemotherapy combined with cetuximab. Stratification by treatment regimens and tumor progression showed mutation rates of 0% (0/13) in Group A, 0% (0/16) in Group B, and 14.3% (3/21) in Group C. In Group C, the mutation rate rose from 0% (0/5) in patients receiving chemotherapy alone to 18.8% (3/16) in those receiving combination therapy. Furthermore, in patients receiving chemotherapy combined with cetuximab of Group B and Group C, longer anti-EGFR treatment duration was associated with a higher mutation rate: 5.9% (1/17) in those treated for ≤ 10 months versus 25.0% (2/8) in those treated for > 10 months. Including one case of secondary BRAF mutation, the cumulative mutation rate reached 37.5% (3/8) in patients with prolonged cetuximab exposure. This study innovatively revealed from multiple perspectives that the crucial role of secondary KRAS mutations in the resistance of mCRC patients to EGFR therapy, emphasizes the importance of continuous genomic monitoring, and provides new ideas for future combination targeted therapies.

It is reported that HER2-low breast cancer (BC) demonstrates a poor response to neoadjuvant chemotherapy (NACT), whereas the response and impact of HER2-low triple-negative breast cancer (TNBC) to NACT remain controversial. TNBC patients who received standard NACT at Tianjin Medical University Cancer Hospital were retrospectively enrolled. The pathological complete response (pCR) rate of NACT were compared between HER2-low and HER2-zero patients. Logistic regression analyses were performed to identify the independent factors affecting the pCR rate in patients with HER2-low TNBC after NACT. We finally included 369 HER2-low and 245 HER2-zero patients with TNBC. The axillary lymph nodes pathological complete response (npCR) rate and total pathological complete response (tpCR) rate after NACT in the HER2-low group were worse than that in the HER2-zero group, and there was no statistical difference in breast pathological complete response (bpCR) between the two groups. In HER2-low TNBC patients, multivariate analysis showed that early clinical lymph node stage, high Ki67 expression, use of immunotherapy and bpCR were independent influencing factors for npCR. Premenopause, small clinical tumor size, early clinical lymph node stage, CK5/6 positivity and EGFR negativity were independent factors affecting tpCR. The npCR and tpCR of HER2-low TNBC patients are worse than those of HER2-zero TNBC patients.

Cold plasma therapy, a revolutionary approach to treating cancer cells, has attracted significant interest due to its capacity to trigger programmed cell death. This study was performed with the aim of investigating the apoptotic effects of A549 and LL/2 lung cancer cells exposed to cold atmospheric pressure plasma (CAP). Herein, the impact of direct helium (He) plasma therapy was evaluated on the programmed cell death of the cancer cell lines at different treatment times ranging from 30 to 180 s. Moreover, as a control to compare with the cancer cells, the normal HUVEC cells were cultured and their cell viability evaluated using the MTT method. The apoptosis was also evaluated in the specific cancer cells using flow cytometry and real-time PCR methods. The treatments were administered at 4, 6, and 8 kV of He-plasma jet. The viability of the cells and SOD activity were assessed at 24 h after the treatment. The results revealed that the observed levels of p53 and caspase-3 genes were in consistent with the results from the MTT assay. The apoptotic effects of He-plasma on A549 and LL/2 cells were induced from altered expressions of p53 and caspase-3 genes which mechanistically taken place via the mitochondrial pathway. Both A549 and LL/2 cancer cells exhibited a substantial rise in apoptosis rates at 4 and 6 kV, while, a noticeable decline was detected at 8 kV. In addition, H2O2 and NO reactive species concentrations in A549 and LL/2 cancer cells treated by He-plasma were measured. It was found that in these cell lines, H2O2 and NO concentrations were significantly high at 6 kV compared to the other discharge voltages. Also, the level of SOD activity in A549 and LL/2 cell lines was significantly reduced at 6 kV. The results imply that the plasma voltage and treatment time should be delicately controlled for selective lung cancer cell killing. This work provides good support for the pre-clinical and clinical treatments of lung cancer through exposure to cold helium plasma that can be used alongside conventional cancer treatments.

In this international collaboration, we examined whether survival in metastatic uveal melanoma is associated with primary tumor size at initial diagnosis. A total of 128 and 205 patients with American Joint Committee on Cancer (AJCC) stage IV disease were included from the Netherlands and Sweden, respectively. Across both cohorts, patients whose tumors had a largest basal diameter ≥ 16 mm or a higher AJCC stage presented with a greater number of hepatic metastases and showed shorter Kaplan-Meier overall survival from the time of metastatic detection. However, this association did not persist after adjustment for the number of hepatic metastases in multivariate Cox regression and a Markov multi-state model. These findings suggest that primary tumor size is associated with survival in metastatic disease and the burden of metastatic lesions at detection, indicating a potential survival benefit of primary tumor treatment. Nevertheless, caution is warranted when interpreting these results, as they differ from some previous reports.

Gastric cancer (GC) is a prevalent digestive tract malignancy, and Huangqi Fuling decoction (HF) has shown potential in enhancing immune function and exhibiting anti-GC activity. However, its mechanisms remain unclear. This study utilized network pharmacology, molecular docking, and in vitro experiments to preliminarily explore the mechanisms by which HF inhibits gastric cancer invasion and metastasis while promoting apoptosis. Public databases identified differentially expressed genes (DEGs), HF targets, and GC-related genes. GO and KEGG analyses revealed signaling pathways. Clinical relevance, immune infiltration, immunotherapy, and molecular docking of hub genes were analyzed. Eight hub genes-PTGS2, MMP9, SELE, CCL2, VCAM1, ICAM1, CXCL2, and CXCL10-associated with the TNF signaling pathway were identified. HF inhibits the invasion and metastasis of GC cells by down-regulating MMP9 and PTGS2 expression, while inducing apoptosis by suppressing BCL-2 expression and promoting BAX expression. Additionally, HF can arrest the cell cycle, blocking AGS cells in the S phase and HGC-27 cells in the G0/G1 phase. This study confirms that HF promotes apoptosis and inhibits metastasis and invasion in GC cells, primarily by modulating the TNF signaling pathway. Additionally, the anti-tumor effects of HF on GC may involve immune regulatory mechanisms, but the mechanism require further experimental verification.

Pleural spread or recurrence of thymic epithelial tumors (TETs) is a tricky puzzle in the clinic and there is currently no recognized effective treatment. This trial evaluated the safety and efficacy of cytoreductive surgery and hyperthermic intrathoracic chemotherapy (S-HITOC) for TETs with pleural spread or recurrence. Here, we reported short-term outcomes of enrolled 45 patients receiving S-HITOC with 25 mg/m2 doxorubicin and 50 mg/m2 cisplatin. The pleural tumor index (PTI) has been proposed for evaluating pleural tumor burden. Treatment-related adverse events of grade ≥3 occurred in eight (17.8%) patients. The pain Visual analog scale (VAS) score was 5.4 ± 1.9 on the 1st day after treatment and was similar to that at baseline level on the 7th day after treatment (p = 0.218). There was no significant difference in the quality of life score (p = 0.676) between baseline and the 60th day after treatment. The estimated 2-year PFS and OS rates were 82.8% and 100.0%, respectively. Subgroup analyses revealed that patients with PTI scores >10 had worse PFS than those with PTI scores ≤10 (p < 0.001). S-HITOC had a manageable complication rate. Early clinical outcomes confirmed that S-HITOC offers encouraging oncological benefits for TETs and satisfactory control of myasthenia gravis. Trial number: NCT05446935.

The interactions between cancer cells and immune cells are crucial regulatory factors in forming the immuno-suppressive microenvironment. However, the underlying regulatory mechanisms remain elusive. In this study, we analyzed hepatocellular carcinoma (HCC) single-cell sequencing of public databases to investigate cellular interactions, revealing that cathepsin E (CTSE) highly expressed cancer cells exhibited significant interactions with T cells. Moreover, lower expression of CTSE is associated with an increased intra-tumoral CD3+ T cell infiltration. Mechanistically, CTSE highly expressed cancer cells upregulated the ubiquinone signaling pathway, enhancing the synthesis and release of des-γ-carboxy prothrombin (DCP), which subsequently activates reactive oxygen species (ROS) production and leads to apoptosis of Jurkat T cells. In vivo, animal experiments show that CTSE knockdown inhibited peripheral blood DCP levels and tumor growth while significantly enhancing the effectiveness of anti-PD-1 immunotherapy. Overall, our data reveal a regulatory mechanism involving CTSE-mediated DCP release and underscore the potential of CTSE knockdown in enhancing anti-PD-1 treatment. Cancer cells with high expression of CTSE upregulate the ubiquinone signaling pathway, promoting the synthesis and release of Des-γ-carboxyprothrombin (DCP). DCP can not only inhibit CD45+ and CD3+ immune infiltration, but also promote T cells to increase the production of reactive oxygen species (ROS), which leads to the increase of T cell apoptosis. CTSE knockdown can inhibit DCP levels and tumor growth, while significantly enhancing the effectiveness of anti-PD-1 immunotherapy.

Oesophageal squamous cell carcinoma (ESCC) is a globally challenging digestive tract malignancy with poor prognosis and limited treatment options. Early-stage ESCC is often asymptomatic, leading to a late-stage diagnosis in many cases. Neoadjuvant therapy combined with surgery is the standard treatment approach for locally advanced ESCC. In recent years, immunotherapy has shown significant efficacy in ESCC. However, various neoadjuvant treatment regimens, including chemotherapy, radiotherapy and immunotherapy, have produced inconsistent outcomes. This study aims to evaluate the efficacy and safety of neoadjuvant chemotherapy (nCT) or neoadjuvant chemoradiotherapy (nCRT) combined with immunotherapy compared with nCRT alone.

Immunotherapy has revolutionised cancer treatment. Immune checkpoint inhibitors have demonstrated significant efficacy across multiple tumour types, including gastric cancer, where several approved programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors show promising antitumour activity. While PD-L1 expression serves as a predictive biomarker for PD-1 inhibitor response, and PD-L1-positive patients generally show better outcomes, therapeutic resistance remains a challenge. Many initial responders eventually develop resistance, and surprisingly, some PD-L1-positive patients fail to achieve expected response rates, indicating emerging resistance mechanisms in potentially responsive populations. Adebrelimab, a PD-L1 inhibitor, demonstrates mechanistic advantages over PD-1 inhibitors, with clinical studies suggesting promising therapeutic potential. When combined with irinotecan, apatinib has shown efficacy in second-line gastric cancer treatment. This study aims to evaluate the efficacy and safety of combining adebrelimab with apatinib and irinotecan for advanced gastric cancer refractory to PD-1 inhibitors.

Atypical hyperplasia (AH) of the breast is a benign proliferative breast disorder that is associated with increased risk of a concurrent, associated breast cancer and an increased future risk of breast cancer. It is often found on screening mammography and in approximately 10% of core needle biopsy specimens. For women with AH, management could include excisional biopsy, enhanced breast cancer surveillance, and risk-reducing medications. More in-depth characterization of AH has recently helped identify a lower risk cohort of women who may be able to avoid surgical intervention at the time of their AH diagnosis. This review updates existing literature on the risk of AH, considerations for surgical excision, management strategies, and mitigation of future risk of breast cancer.

Pityriasis rubra pilaris (PRP) is a rare, inflammatory cutaneous disorder of unknown aetiology, and its association with inflammatory joint disease has not been well established. The lack of definitive evidence or clear guidelines makes PRP treatment difficult. Our patient presented with multiple large non-melanoma skin cancers (NMSCs) and a progressive cutaneous eruption consistent with PRP. NMSCs on presentation were found to be five basal cell carcinomas (BCCs), one squamous cell carcinoma and one invasive carcinoma with basaloid and squamous differentiation to skeletal muscle requiring radiation. His course was complicated by arthritis and reactive lymphadenopathy. Our patient saw slow improvement in his rash after treatment with ixekizumab and multiple Mohs surgeries for removal of his BCCs with decreased pruritus, erythema and hyperkeratosis. PRP-associated arthritis is a rare component of the primarily dermatologic disorder, and it is important for clinicians to be aware of this association to adequately address joint manifestations.

Metastatic spread of breast cancer to the gastrointestinal (GI) tract is uncommon. When it does occur, it is typically associated with invasive lobular carcinoma and most often involves the stomach and intestinal wall, though the colon may be involved in rare instances. We present a unique case of metastatic breast cancer diagnosed via a colonic polyp found during routine screening colonoscopy. This case illustrates an unusual presentation of metastatic breast cancer.

This cross-sectional study enrolled 70 women aged 18-40 years in Baqubah City (Iraq), from September to November 2024. Participants were divided into two age-matched groups: a control group (n=35, healthy nulliparous women) and a patient group (n=35, physician-diagnosed breast cancer cases). Blood samples were collected from both groups, processed via centrifugation, and analyzed for key biochemical markers, including the tumor antigen CA15-3, apelin, sex hormones (estrogen, progesterone, etc.), and essential minerals (e.g., calcium, zinc). Statistical analysis revealed highly significant differences (p ≤ 0.001) in serum biomarker levels between breast cancer patients and controls. Elevated CA15-3 and altered apelin concentrations were observed in cancer patients, alongside dysregulated sex hormones and mineral imbalances. These findings underscore the potential diagnostic utility of these biomarkers in breast cancer and highlight metabolic disruptions associated with the disease. Further research is warranted to validate their clinical applicability.

Endometrial hyperplasia (EH) is a gynecological disease characterized by pathological overgrowth of the endometrium as a result of the unhindered action of estrogens. The relevance of studying this disease is based on the morbidity rate of this disease in women in the Republic of Kazakhstan, which, in the absence of timely diagnosis, treatment and dynamic monitoring, may lead to the rapid progression to endometrial cancer (EC).

This article describes an uncommon clinical case of a 71-year-old patient diagnosed with pulmonary artery intimal sarcoma, which presented as a significant pulmonary embolism complicated with acute cor pulmonale. The diagnosis was confirmed via histological and immunohistochemical examination, verifying the tumor's mesenchymal characteristics. This article underscores the criticality of early detection and timely surgical intervention when a malignant pulmonary artery tumor is detected, as it poses a substantial risk to the patient's life. Given that these rare cancers can mimic more common illnesses like pulmonary embolism in their symptoms, this instance emphasizes the difficulties in detecting them. Appropriate diagnosis and treatment depend on early detection by sophisticated imaging and histological confirmation.

Giant mucinous cystadenomas are rare in adolescents and young adults.

The benefit of regional nodal irradiation in the treatment of breast cancer is well established for patients with pathologically positive axillary nodes, but whether it is also beneficial for patients whose nodes become pathologically tumor free (ypN0) after neoadjuvant chemotherapy remains unclear.

Recurrence occurs in 20%-30% of early-stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Hypoxia in the tumor microenvironment drives radiation resistance, immune evasion, and tumor progression. Biomarkers measuring hypoxia may be useful for prognostication of NSCLC treated with SBRT. We investigate an RNA-based approach to measure tumor hypoxia and associate these molecular biomarkers with clinical outcomes after SBRT.