Cancer Management and Research最新文献

Purpose: To explore the effect of DSG2 on the growth of cervical cancer cells and its possible regulatory mechanism.

Methods: The expression levels and survival prognosis of DSG2 and ADAM17 in cervical squamous cell carcinoma tissues and adjacent normal tissues were analyzed by bioinformatics. CCK-8 assay, colony formation assay and Transwell assay were used to detect the effects of DSG2 on the proliferative activity, colony formation ability and migration ability of SiHa and Hela cells. The effect of DSG 2 on the level of ADAM17 transcription and translation was detected by qPCR and Western blot experiments. The interaction between DSG2 and c-MYC was detected by immunocoprecipitation. c-MYC inhibitors were used in HeLa cells overexpressing DSG2 to analyze the effects of DSG2 and c-MYC on proliferation, colony formation and migration of Hela cells, as well as the regulation of ADAM17 expression.

Results: DSG2 was highly expressed in cervical squamous cell carcinoma compared with normal tissues (P<0.05), and high DSG2 expression suggested poor overall survival (P<0.05). After DSG2 knockdown, the proliferative activity, colony formation and migration ability of SiHa and Hela cells were significantly decreased (P<0.05). Compared with adjacent normal tissues, ADAM17 was highly expressed in cervical squamous cell carcinoma (P<0.05), and high ADAM17 expression suggested poor overall survival in cervical cancer patients (P<0.05). The results of immunocoprecipitation showed the interaction between DSG2 and c-MYC. Compared with DSG2 overexpression group, DSG2 overexpression combined with c-MYC inhibition group significantly decreased cell proliferation, migration and ADAM17 expression (P < 0.05).

Conclusion: DSG2 is highly expressed in cervical cancer, and inhibition of DSG2 expression can reduce the proliferation and migration ability of cervical cancer cells, which may be related to the regulation of ADAM17 expression through c-MYC interaction.

Purpose: As one of the most important breakthroughs in cancer therapy, immune checkpoint inhibitors have greatly prolonged survival of patients with breast cancer. However, their application and efficacy are limited, especially for advanced HER2-negative breast cancer. It has been reported that epigenetic modulation of the histone deacetylase (HDAC) inhibitor chidamide, as well as immune microenvironment modulation of radiotherapy are potentially synergistic with immunotherapy. Thus, the combination of chidamide, radiotherapy and immunotherapy is expected to improve prognosis of patients with advanced HER2-negative breast cancer.

Patients and methods: This is a single-arm, open, prospective clinical trial investigating the efficacy and safety of the combination of HDAC inhibitor chidamide, anti-PD-1 antibody sintilimab, and the novel immuno-radiotherapy, which aims to enhance efficacy of immunotherapy, in subsequent lines of therapy of HER2-negative breast cancer. Our study will include 35 patients with advanced breast cancer that has failed endocrine therapy and first-line chemotherapy. Participants will receive 30 mg of chidamide twice a week, 200 mg of sintilimab once every 3 weeks, combined with immuno-radiotherapy. Radiotherapy will be centrally 8 Gy for at least one lesion, and at least 1 Gy for the other lesions. We will complete three fractions of radiotherapy in one cycle. The primary endpoint is progression-free survival, and secondary endpoints are objective response rate, disease control rate and safety. Moreover, biomarkers including cytokines and lymphocyte subgroups will be explored.

Conclusion: As a single-arm clinical trial, the analysis of the influence of each single treatment is limited. Besides, our study is an open study, which involves neither randomization nor blinding. In spite of the abovementioned limitations, this prospective clinical trial will give an insight into subsequent lines of therapy of HER2-negative advanced breast cancer, prolong the survival or achieve long remission for these participants, and identify potential responders.

Purpose: In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.

Patients and methods: A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.

Results: 19 patients in our center's MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).

Conclusion: The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.

Background & aims: The objective of this study was to evaluate the prognostic nutritional index (PNI) as a predictor of short-term postoperative complications in esophageal squamous cell carcinoma patients undergoing neoadjuvant immunochemotherapy.

Methods: Clinical data were collected from 77 patients undergoing radical esophageal cancer surgery after neoadjuvant immunochemotherapy at Tongji Hospital from January 2022 to January 2023. The receiver operating characteristic curve (ROC) was utilized to establish the optimal cut-off point for the PNI. Subsequently, patients were stratified into low and high PNI groups according to this cut-off point, and comparisons were made between the two groups in terms of clinical data and postoperative complications.

Results: Out of the 77 patients included in the study, 31 were categorized in the low PNI group and 46 in the high PNI group, with a defined cutoff point of 47.38. Significant statistical variances were noted in the occurrence rates of general complications (P < 0.001), pulmonary infections (P < 0.001), and anastomotic fistula (P = 0.034) between the two groups. The low PNI group displayed elevated rates of these complications in comparison to the high PNI group.

Conclusion: The research findings indicate that preoperative nutritional assessment using the PNI can effectively predict short-term postoperative complications in esophageal squamous cell carcinoma patients who have undergone neoadjuvant therapy. Furthermore, the results suggest that implementing nutritional interventions for patients with moderate-to-severe malnutrition, as indicated by preoperative PNI evaluation, may help reduce the incidence of postoperative complications.

Purpose: There is a lack of evidence regarding how patients with malignant brain tumor and their relatives experience participation in neurooncological clinical trials. Similarly, insights from the perspective of trial staff caring for this group of patients are missing. This study aims to investigate patient, relative and trial staff experiences regarding participation in clinical neurooncological trials.

Methods: Within a qualitative exploratory study, 29 semi-structured interviews with brain tumor patients, relatives and trial staff were conducted and analyzed using reflexive thematic analysis (RTA) by Braun and Clarke. A patient researcher and patient council were involved in data analysis and interpretation.

Results: Four themes were developed reflecting significant aspects of the trial experience: 1. "It all revolves around hope"; 2. "Trial participation: experiencing unique medical care"; 3. "Everyone's roles are changing"; 4. "Communication as a possible area of conflict". Experiencing trial participation and general medical treatment were found to be interconnected to such a degree that they were often not meaningfully distinguished by patients and relatives.

Conclusion: In addition to assessing traditional endpoints for patient outcomes, we recommend increased emphasis on investigating the impact of the "soft" components constituting trial participation. Due to the interconnectedness of medical treatment and trial participation, we recommend further investigation in comparison to experiences in regular care. A deeper understanding of trial participation is needed to inform improvements for patient experiences and staff satisfaction alongside medical and scientific progress.

Aim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels.

Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro.

Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS (33.6±3.9 versus 39.6±3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2±3.4 versus 15.4±1.7, p=0.002) and DFS (31.0±3.1 versus 12.4±1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7±3.4 versus 16.2±1.9, p=0.026) and DFS(30.7±3.0 versus 11.8±2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8±3.0 versus 12.6±2.3, p=0.053). Patients with preoperative CA19-9 values ≤467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values >467 U/mL (37.9±4.1 versus 22.9±4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4±4.0 versus 31.5±3.9, p=0.001) and DFS(35.7±4.0 versus 20.6±2.7; p<0.0001) in the Gemcitabine subgroup.

Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.

[This retracts the article DOI: 10.2147/CMAR.S264358.].

[This retracts the article DOI: 10.2147/CMAR.S260693.].

Background: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified.

Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells.

Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities.

Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management.

Desmoid tumors (DT) are rare, intermediate-grade sarcomas characterized by locally aggressive growths that commonly occur intra-abdominally, in the abdominal wall, or in the extremities. Desmoid tumors are 2-3-fold more common in females than males, with most patients aged <40 years at diagnosis. Clinical course of DT is highly variable but rarely fatal, with median overall survival >80% at 20 years. However, patient morbidity and DT symptom burden can be high. DT significantly reduce patient quality of life, imposing substantial physical, emotional, and social burdens. Pain, fatigue, and insomnia are common symptoms; disfigurement, mobility restrictions, and, rarely, the need for amputation may also result. Despite its limited impact on survival, patients with DT may have anxiety and depression levels commensurate with those associated with malignant sarcomas. Thus, DT impose an array of significant, long-term morbidities on a young patient population. In order to evaluate the impact of these morbidities, patient-reported outcome (PRO) tools are used, which assess outcomes of importance to patients that extend beyond traditional oncology endpoints. General or oncology-related PROs can be used; although currently, the only DT-specific, validated PRO measure is the GOunder/Desmoid Tumor Research Foundation DEsmoid Symptom/Impact Scale (GODDESS^©), consisting of an 11-item DT Symptom Scale (DTSS) and a 17-item DT Impact Scale (DTIS). DTSS and DTIS were secondary endpoints in DeFi, a randomized phase 3 trial of nirogacestat; blinded, pooled data from DeFi were used to validate GODDESS reliability and responsiveness as a PRO measure in DT. Another DT-specific PRO measure, the Desmoid-Type Fibromatosis Quality of Life (DTF-QoL) questionnaire, has been developed but not validated. As novel DT therapies continue to be developed, incorporating DT-specific PRO measures into clinical trials will be key to capturing patient voice, improving outcomes of importance to this unique patient population, and assisting patients and providers in selecting optimal treatment.