Current Issue : January-March Volume : 2024 Issue Number : 1 Articles : 5 Articles
Background Low grade glioma (LGG) is considered a heterogeneous tumor with highly variable survival and limited efficacy of immunotherapy. To identify high-risk subsets and apply immunotherapy effectively in LGG, the status and function of immune infiltration in the glioma microenvironment must be explored. Methods Four independent glioma cohorts comprising 1,853 patients were enrolled for bioinformatics analysis. We used ConsensusClusterPlus to cluster patients into four different immune subtypes based on immune infiltration. The immune-infiltration signature (IIS) was constructed by LASSO regression analysis. Somatic mutation and copy number variation (CNV) analyses were performed to explore genomic and transcriptomic traits in the high- and low- risk groups. The correlation between response to programmed cell death 1 (PD-1) blockade and the IIS risk score was confirmed in an in vivo glioma model. Results Patients were clustered into four different immune subtypes based on immune infiltration, and the high immune infiltration subtype was associated with worse survival in LGG. The high immune infiltration subtype had stronger inflammatory response, immune response and immune cell chemotaxis. The IIS, consisting of EMP3, IQGAP2, METTL7B, SLC1A6 and TNFRSF11B, could predict LGG malignant progression, which was validated with internal clinical samples. M2 macrophage infiltration positively correlated with the IIS risk score. The high-risk group had significantly more somatic mutations and CNVs. The IIS risk score was related to immunomodulatory molecules and could predict immunotherapy clinical benefit. In vivo, immunotherapy-sensitive glioma model exhibited higher IIS risk score and more infiltration of immune cells, especially M2 macrophages. The IIS risk score was decreased in an immunotherapy- sensitive glioma model after anti-PD1 immunotherapy. Conclusion Different immune subtypes of LGG had unique immune cell infiltration characteristics, and the high immune infiltration subtype was associated with immunosuppressive signaling pathways. A novel IIS prognostic model based on immune infiltration status was constructed for immunophenotypic classification, risk stratification, prognostication and immunotherapy response prediction in LGG....
Background Non-metastatic breast cancer treatment is mainly based on surgery, with or without chemotherapy, radiotherapy and/or hormone therapy. To reduce the risk of hormone receptor positive (HR+) disease recurrence, hormone therapy is prescribed for at least 5 years. It may induce adverse drug reactions (ADRs) as joint pain, sexual dysfunction, weight increase, fatigue, mood disorders and vasomotor symptoms. Around 30–40% of patients withhold hormone therapy within 5 years after initiation. Based on encouraging results of mobile health in patient follow-up, we developed a web-application addressed for breast cancer patients initiating adjuvant hormonal therapy and aimed to assess its impact on hormone therapy adherence, ADRs management, and health-related quality of life. Methods The WEBAPPAC trial is a randomized, open-label, prospective, single-center phase 3 study aiming to assess the interest of a web-application support as compared to standard management among breast cancer patients initiating hormone therapy. The main endpoint is the proportion of patients with hormone therapy adherence failure within 18 months after treatment start, in each arm. Eligible patients will be 1:1 randomized between the WEBAPPAC web-application support (experimental arm,) or standard support (control arm), with stratification on type of hormone therapy (Aromatase inhibitor or Tamoxifen). We plan to enroll 438 patients overall. Failure to hormone therapy will be assessed using the Morisky 8-item self-questionnaire (MMSA8), patient adherence logbook, and medical consultations. Secondary outcomes include hormone therapy adherence at 6 months, pain (Visual Analogue Scale and Brief Pain Inventory), quality of life (EORTC QLQ-C30 and BR23 self-questionnaires), anxiety and depression (Hospital and Depression Scale), and return to work and/or daily activities. The user experience with the WEBAPPAC web-application will be assessed using the System Usability Scale (SUS) questionnaire. Discussion Hormone therapy discontinuation or adherence failure in breast cancer patients may be indirectly related to an increased risk of recurrence. A better control of medication adherence, through the detection of side effects and some proposed actions trying to reduce them, appears therefore essential to limit the risk of disease recurrence. The WEBAPPAC web-application thus aims better monitoring and allowing higher level of responsiveness in case of ADRs, thus improving treatment adherence....
Background Cervical cancer (CC) can be prevented through early detection facilitated by screening as well as an early diagnosis and effective treatment of the precancerous lesions. The present research aimed to determine the predictors of cervical cancer screening (CCS) based on the PEN-3 model constructs. Methods A cross-sectional study was conducted between September 2021- March 2022 with 840 women aged 15–49 in the city of Bandar Abbas, in the south of Iran, using a cluster sampling. The participants completed a valid and reliable self-administered questionnaire in person. The questionnaire included demographic characteristics, knowledge toward CC and the constructs of the PEN-3 model toward CCS. A multivariable logistic regression was used to determine the relationship and predictive power of model constructs with behavior as an outcome variable. The data were statistically analyzed in STATA 14.2. The p-value < 0.05 was considered statistically significant. Results A total of 810 questionnaires were analyzed (with a return of 95.63%). The mean and standard deviation of the participants’ age was 30.97 ± 5.80 years. Pearson correlation coefficient analysis of all constructs and CCS behavior was statistically significant (P-value < 0.05). The multivariable logistic regression analytic results were enablers toward CCS (coefficient: 0.275) and Nurturers toward CCS (coefficient: 0.182), perceptions toward CCS (coefficient: 0.077) and knowledge toward CC (coefficient: 0.048, marginal significant) were predictors of CCS behavior. For the internal validity of the designed prediction model, a sample of 1000 was selected using the bootstrap sample replacement method which demonstrated the accuracy of the model PEN-3 is about 75% in predicting CCS behavior. Conclusions The results of the present research showed that personal factors such as perceptions and interpersonal factors such as enablers and nurturers toward CCS can predict CCS behavior. Therefore, in order to increase the acceptance of CCS in women, a set of intrapersonal and interpersonal factors should be taken into account....
Background The centromere protein O (CENPO) is an important member of the centromere protein family. However, the role of CENPO in pan–cancer and immune infiltration has not been reported. Here, we investigated the role of CENPO in pan–cancer and further validated its role in lung adenocarcinoma (LUAD) by in vitro experiments. Method The UCSC Xena database and The Cancer Genome Atlas (TCGA)–LUAD data were used to assess the expression levels of CENPO. The potential value of CENPO as a diagnostic and prognostic biomarker for pan–cancer was evaluated using TCGA data and the GEPIA database. The -expression profiles of LUAD patients and the corresponding clinical data were downloaded for correlation analysis. The role of CENPO in immune infiltration was investigated using the UCSC Xena database. Subsequently, qRT–PCR was performed to detect the expression of CENPO. Cell proliferation, migration, and invasion were determined using CCK–8, wound–healing assay, and transwell assay, respectively. Results CENPO is highly expressed in most cancers, and the upregulation of CENPO is associated with poor prognosis in many cancers. CENPO expression correlates with age, TNM stage, N stage, T stage, and receipt of radiotherapy in LUAD patients, and LUAD patients with high CENPO expression have poorer overall survival (OS) and disease–free survival (DFS). In addition, CENPO expression is associated with immune cell infiltration and immune checkpoint inhibitors. Moreover, the expression of CENPO was closely related to the expression of tumor mutational load and microsatellite instability. In vitro experiments showed that CENPO expression was increased in LUAD cell lines and that knockdown of CENPO significantly inhibited the proliferation, cell invasion, and migration ability of LUAD cells. Conclusion CENPO may be a potential pan–cancer biomarker and oncogene, especially in LUAD. In addition, CENPO is associated with immune cell infiltration and may serve as a new molecular therapeutic target and effective prognostic marker for LUAD....
Background For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established. Therefore, the aim of this trial was to investigate whether preoperative short-course radiotherapy followed by chemotherapy with four cycles of CAPOX can double the pCR rate compared to a standard schedule of long-course preoperative CRT in patients with LARC. Methods This is a multi-centre, prospective, open label, randomised controlled trial. Patients with clinical primary tumour stage 3 and higher or regional node-involved rectal cancer located within 10 cm from the anal verge were randomly assigned equally to short-course radiotherapy (25 Gy in 5 fractions over 1 week) followed by four cycles of CAPOX (intravenous oxaliplatin [130 mg/m2, once a day] on day 1 and capecitabine [1,000 mg/m2, twice a day] from days 1 to 14) (TNT) or CRT (50.4 Gy in 28 fractions over 5 weeks, concurrently with concomitant oral capecitabine 825 mg/m2 twice a day). After preoperative treatment, total mesorectal excision was performed 2–4 weeks in the TNT group and 6–10 weeks in the CRT group, followed by optional additional adjuvant chemotherapy. The primary endpoint is the pCR rate, and secondary endpoints include disease-related treatment failure, quality of life,and cost-effectiveness. Assuming a pCR rate of 28% and 15% in the TNT and CRT groups, respectively, and one-side alpha error rate of 0.025 and power of 80%, 348 patients will be enrolled considering 10% dropout rate. Discussion The TV-LARK trial will evaluate the superiority of employed TNT regimen against the standard CRT regimen for patients with LARC. We aimed to identify a TNT regimen that will improve the pCR rate and decrease systemic recurrence in these patients. Trial registration Cris.nih.go.kr ID: KCT0007169 (April 08, 2022). The posted information will be updated as needed to reflect the protocol amendments and study progress....
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