Renal cell carcinoma (RCC) is the most common solid-organ malignancy in Western countries, and upper tract urothelial carcinoma (UTUC) is the most common malignancy in Asian countries. The management of RCC/UTUC in kidney transplant recipients is complex and clinically challenging due to post-transplant modifications associated with immunosuppressive treatment. This retrospective study evaluated the incidence, risk factors, treatment outcomes, and oncological implications of RCC and UTUC in kidney transplant recipients from 2008 to 2023. Data were collected from clinical records, and follow-up calls for 20 patients diagnosed with RCC and UTUC among 2,283 kidney transplant recipients, revealing an incidence rate of 0.78% for RCC (18 patients) and 0.087% (two patients) for UTUC. Most patients presented localized disease at diagnosis. Surgical interventions included radical nephrectomy for the native kidney's RCC, radical or partial nephrectomy for allograft RCC, and radical nephroureterectomy for UTUC in the native kidney and allograft. Oncological outcomes indicated a mean follow-up of 51.29 months, during which five patients (25%) developed metastases, which achieved prolonged survival through surgical management, adjuvant therapy, and immunosuppression adjustments. The study highlights the increased cancer risk in this population and underscores the necessity for established screening protocols and individualized treatment strategies to optimize patient outcomes while preserving kidney function. These findings contribute to the ongoing research on managing malignancies in transplant recipients, with implications for further research and clinical guidelines.

ObjectiveCheckpoint inhibitor pneumonitis (CIP) is a potentially life-threatening immune-related adverse event. Efficient strategies to select patients at risk are still required. The aim of our study was to assess the utility of a machine learning model, integrating pre-treatment CT lung radiomics features with clinical data, to predict patients at risk of developing CIP.MethodsIn this retrospective study, 116 patients with varied malignancies treated with immune checkpoint inhibitors (ICIs) were included. In this cohort, 35 patients presented with CIP and 81 patients did not. Each lung and its lobes were segmented on pre-treatment CT scans to perform a handcrafted radiomic analysis. Radiomic features were associated with clinical parameters to build generalized linear (GLM) and random forest (RF) models, to predict occurrence of CIP. The models were fine-tuned, validated and tested using a nested 5-fold cross-validation method.ResultsThe RF models combining radiomic and clinical features showed the best performances with an area under the ROC curve (AUC) of 0.75 (95%CI:0.62-0.88) on the test set. The most accurate clinical model was a RF model and achieved an AUC of 0.72 (95%CI:0.51-0.92). The best radiomic model was a GLM model and achieved an AUC of 0.71 (95%CI:0.58-0.84).ConclusionsOur CT-based lung radiomic models showed moderate to good performance at predicting CIP. We demonstrated the potential role of machine learning models associating clinical parameters and lung CT radiomic features to better identify patients treated with ICIs at risk of developing CIP.Advances in knowledge: Radiomics analysis of the lung parenchyma could be used as a non-invasive tool to select patients at risk of developing immune-checkpoint pneumonitis.

Lung adenocarcinoma remains a significant public health concern, necessitating novel therapeutic approaches. Neuregulin 4 (NRG4), a secreted protein of the epidermal growth factor family, is recognized for its roles in metabolic regulation and anti-inflammatory processes, suggesting therapeutic potential across various diseases. However, its specific function in lung adenocarcinoma progression is not well elucidated. Methods: We utilized The Cancer Genome Atlas (TCGA) database to examine correlations between NRG4 expression, epithelial-mesenchymal transition (EMT)-related genes, and overall survival in lung adenocarcinoma patients. The effects of recombinant NRG4 (rNRG4) on cell migration and cancer progression were evaluated through Transwell assays, quantitative PCR, immunofluorescence, and immunohistochemistry. Additionally, a lung adenocarcinoma mouse model (LLC-bearing) was employed to assess the impact of rNRG4 on tumor progression. RNA sequencing of primary tumors was conducted to explore the functional mechanisms underlying rNRG4's effects. Results: Our analysis revealed that NRG4 expression inversely correlates with key molecules involved in cell migration and EMT in lung adenocarcinoma. Treatment with rNRG4 significantly inhibited cell proliferation, migration, EMT, and tumor growth in both in vitro and in vivo models. RNA sequencing indicated that rNRG4 downregulates extracellular matrix (ECM) proteins, and online database analyses confirmed that higher NRG4 expression is associated with reduced ECM levels and improved patient survival. Conclusions: These findings suggest that NRG4 serves as a potential candidate for further investigation for lung adenocarcinoma.

ZNF384 is a C2H2-type zinc finger protein (ZNF) which is implicated in DNA double-strand break (DSB) repair through the classical non-homologous end-joining (cNHEJ) pathway.

V-set and immunoglobulin domain containing 4 (VSIG4) is a B7-family-related protein almost exclusively expressed on macrophages. The difference in its expression mediates the dynamic transformation of the polarization state of macrophages, but the underlying mechanism is still unclear. We sought to reveal the correlation between VSIG4 and the polarization of tumour-associated macrophages (TAMs) and the immune escape of tumour cells in colorectal cancer (CRC).

Evernic acid (EA) has emerged as a potential therapeutic agent with its low toxicity and anticancer properties. In this study, the anticancer effect of EA on ovarian cancer cell lines and normal ovarian surface epithelial cells (OSE) was evaluated. The antiproliferative effect of EA was evaluated by xCELLigence Real-Time Cell analysis, colony formation assay, and acridine orange and DAPI staining methods. Genotoxicity analysis was performed by comet assay. The effect of EA on cell migration was analyzed by wound healing assay. The potential of EA to induce apoptosis was also determined by evaluating the changes in gene and protein expression levels by qRT-PCR and Western blot analysis, respectively. EA was found to be a promising potential therapeutic agent for ovarian cancer without showing significant cytotoxic effect on normal cells. Furthermore, EA decreased the ability of ovarian cancer cells for migration, increased the rate of apoptosis by inhibiting BIRC5 and activating CASP3, triggered cell cycle arrest in the G2/M phase, and caused a decrease in mitochondrial membrane potential and genotoxic effects. The results have shown that EA could be an effective candidate molecule for ovarian cancer treatment.

The thoracoscopic management of hilar calcified lymph nodes is a technical challenge as the dense adhesions with the bronchus and vessels prevented a safe dissection. Herein, we reported the unexpected bleeding after firing the mediastinal trunk of the pulmonary artery with calcified lymph nodes during the completion of thoracoscopic right upper lobectomy for the management of lung cancer. The bleeding was successfully fixed by an emergent thoracotomy. We used a standard white vascular cartridge that probably was unable to staple a thick tissue, such as the vessel with calcified lymph node. Thus, the best strategy remained to cut the pulmonary artery where the lymph nodes were not attached, and the plasty of the pulmonary artery should be considered if the lymph nodes could not be dissected from the vessels. If the surgeons were not confident to manage this situation under thoracoscopy, conversion to thoracotomy should never be forgotten. Open surgery could facilitate the dissection of calcified lymph nodes and safely fix unexpected bleeding due to vascular lesions.

To explore the feasibility, safety, and effectiveness of brachytherapy of locally advanced bladder cancer, clinical data of 86 patients with locally advanced bladder cancer treated in the Department of Urology Surgery, Shanxi Provincial Cancer Hospital, between January 2015 and June 2019 were analyzed retrospectively. The patients were categorized into the study (n = 45) and control (n = 41) groups according to the treatment methods. Patients in the study group were treated with brachytherapy (intraoperative implantation of radioactive particles) + neoadjuvant chemotherapy (NAC), and those in the control group were treated with NAC. Patients in both groups underwent radical cystectomy (RC) + pelvic lymph node dissection. Postoperative pathological examinations proved that patients in both groups had urothelial carcinoma at stage pT3-pT4. The endpoints included 3-y locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), and adverse events after treatment. The efficacy and safety of interstitial implantation of radioactive particles for the treatment of locally advanced bladder cancer were assessed. The patients were followed up for 9-42 months. The 3-y LRFS was significantly higher in the study group (88.9%) than in the control group (60.9%) (p = .003). The 3-y DMFS in the study group (71.1%) and the control group (73.2%) was statistically similar (p = .945). The 3-y DFS and OS were not statistically significant between the two groups (DFS: study group 64.4% vs. control group 51.2%, p = .073; OS: study group 66.7% vs. control group 58.5%, p = .180). Local shifting of the particles was detected in three patients at 1 week to 1 month after the operations in the study group, but no related complications were observed. Blood events (anemia, leukocytopenia, and thrombocytopenia), liver and renal dysfunction, vomiting, diarrhea, and weakness were the major adverse reactions, which were alleviated after symptomatic treatments. The results have not statistically significant differences between the two groups in major adverse reactions. Compared to the NAC group, brachytherapy + NAC significantly prolongs the LRFS of patients with locally advanced urothelial bladder carcinoma who underwent RC + pelvic lymph node dissection. This surgery increases the LRFS, develops better personalized treatment plans, and improves treatment effectiveness. In addition, the treatment is safe and effective, with only limited adverse effects.

Acral lentiginous melanoma (ALM) is a rare and insufficiently understood subtype of melanoma lacking in effective treatment options. Recent work has demonstrated that the response of ALM to immune checkpoint blockade is inferior to that of cutaneous melanoma (CM). Here we performed bulk genomic and transcriptomic sequencing of tumor tissue from 28 ALM and 5692 CM cases. Similar to prior studies, ALM was associated with a significantly lower incidence of point mutations, including in the TERT promoter and BRAF, but increased numbers of gene amplifications, notably of CCND1, HMGA2, and MDM2. Reactome pathway analysis revealed enhancement of keratinization and PI3K/AKT signaling pathways. Overall immunogenicity was decreased in ALM, which possessed lower IFNγ (p < 0.001) and T-cell inflammatory (p = 0.03) pathway scores than CM. Despite higher computationally inferred levels of myeloid dendritic cells (p = 0.006), neoantigen load independent of predicted HLA binding affinity was lower (p < 0.01) in ALM versus CM. Assessment of classical and nonclassical HLA mRNA levels revealed upregulation of HLA-G, suggesting alternative ALM immune evasion pathways in the setting of lower PD-L1 expression (p = 0.005). Additional research is needed to better understand and therapeutically target signaling networks in the ALM tumor microenvironment.

Breast cancer (BC) has a poor prognosis due to metastasis and recurrence. LINC01158 is aberrantly expressed in breast cancer. Therefore, we investigated the regulatory mechanism and prognostic value of LINC01158 in BC.

The mechanism by which circRERE (hsa_circ_0006837) modulates the malignant progression of gastric cancer was investigated to identify a novel biomarker and therapeutic target for this disease.

Mammography screening has improved early breast cancer detection, leading to reduced mortality and lower rates of advanced breast cancer. However, mammography has a high false positive rate that results in over a million invasive breast biopsies of benign lesions in the US each year. Therefore, there is a need for noninvasive, blood-based diagnostics that can accurately assess risk of malignancy for women with indeterminate lesions identified by mammography, such as BI-RADS category 4 breast lesions. The aim of this study is to identify biomarkers from multiplexed extracellular vesicle liquid biopsy that can accurately classify mammographically detected BI-RADS 4 lesions.

Non-small cell lung cancer (NSCLC) is a significant global health challenge, with 2% of cases fuelled by RET rearrangements. RET inhibitors (RETi) have revolutionized treatment for these patients, but resistance remains an important clinical challenge limiting therapy effectiveness. This study investigated the mechanisms underlying resistance to RETi.

Breast cancer neoadjuvant therapy may negatively impact the immune system. As a secondary outcome of the docosahexaenoic acid (DHA) for women with breast cancer in the neoadjuvant setting (DHA-WIN trial), we sought to assess the effects of an intervention with DHA on parameters of immune function of women undergoing neoadjuvant therapy.

We investigated whether germline BRCA1/2 pathogenic variants (PVs) influence treatment response and survival outcomes in breast cancer patients treated with neoadjuvant chemotherapy (NCT). Using propensity score matching (PSM) to control for variations in treatment and clinicopathological characteristics, this study aimed to evaluate the influence of BRCA1/2 mutations on prognosis and treatment efficacy, providing insights for optimizing therapeutic strategies and improving patient outcomes.

Recent advancements in the understanding of lower rectum anatomy, rectal cancer biology, and surgical techniques have emphasized the importance of radical surgery for low rectal cancer that balances oncological safety and anal function preservation. After total mesorectal excision (TME) and coloanal anastomosis, participants face high risks of anastomotic leakage and infection, often requiring a protective ileostomy. However, ileostomies themselves lead to significant complications, such as dehydration and chronic renal failure, and many participants cannot have their stomas reversed as planned. The Turnbull-Cutait procedure, involving delayed transanal pull-through rectal resection, has emerged as a safer alternative, reducing leakage complications and avoiding the need for a protective stoma. Recent studies support its use in challenging rectal cases, showing comparable or better outcomes than standard techniques. Despite these promising results, limited data exists on its application to intersphincteric resection (ISR) or intersphincteric dissection (ISD), which itself has higher complication rates. Therefore, further research is needed to evaluate this Turnbull-Cutait anastomosis procedure (delayed transanal pull-through) in ISR, comparing its complications, oncological outcomes, and functional results to those of traditional methods (direct anastomosis). This study is a prospective, multicenter, 1:1, non-inferiority, randomized controlled trial with 110 participants, divided into two groups: the staged Turnbull-Cutait pull-through anastomosis group (n = 55) and the direct anastomosis group (n = 55). The control group will undergo ISR with traditional anastomosis plus protective ileostomy, while the experimental group will receive the transanal pull-through and delayed anastomosis without ileostomy. The primary outcome is the 30-day overall postoperative complication rate, including anastomotic leakage, infection, and other complications. Secondary outcomes include long-term complications, total surgery time, anorectal function (measured by LARS and Wexner scores), urinary and sexual function, quality of life (EORTC QLQ-CR29 and FIQL), and 3-year disease-free survival (DFS) and overall survival (OS).

Lemur Tail Kinase 3 (LMTK3) promotes cell proliferation, invasiveness and therapy resistance, and its expression correlates with poor survival in several different malignancies, including breast cancer. Crosstalk through extracellular vesicles (EVs) is an increasingly appreciated mechanism of cell communication within the tumour immune microenvironment, which contributes to different aspects of cancer progression and plays a pivotal role in shaping tumour fate.

SMARCA4 and SMARCA2, mutually exclusive catalytic ATPase subunits of human mammalian Switch/Sucrose-Nonfermentable chromatin remodeling enzymes, function as tumor suppressor genes. SMARCA4-deficient adenocarcinoma (SMARCA4-dADC) is a relatively rare subtype of TTF1/P40-negative non-small cell lung cancer. The concurrent presentation of SMARCA4-dADC and poorly differentiated adenocarcinoma with SMARCA2 (also known as BRM) loss in separate lobes of the same patient is even less common. This report describes such a case involving the simultaneous occurrence of these two tumor types in distinct locations within the lungs.

Outcomes in glioblastoma are improved by surgical resection and adjuvant radiation (RT). In primary GBM (pGBM), large clinical target volume (CTV) margins typically cover occult invasion. In recurrent GBM (rGBM), RT often uses tiny CTV margins that likely omit occult invasion due to re-RT radiation necrosis concerns. Whole-brain spectroscopic MRI (sMRI) is an emerging technique with similar resolution to PET that may help define the CTV for rGBM.

HBV integration is considered as the main contributor to hepatocellular carcinoma (HCC). However, whether HBV integrated sequences determine genotype pathogenicity and how to block their function during HCC progression remains unclear.