Clinical Medicine Insights-Oncology最新文献

Background: Triple-negative breast cancer (TNBC) lacks effective targeted therapies, underscoring the need for novel molecular targets. Gonadotropin-releasing hormone receptor (GnRHR) has been shown to suppress TNBC proliferation and metastasis. G protein-coupled receptor 173 (GPR173), known to regulate GnRHR in neuroendocrine cells, has an undefined role in TNBC. This study aimed to determine whether GPR173 modulates TNBC progression through GnRHR-mediated signaling.

Methods: GPR173 and GnRHR expression levels were analyzed in TNBC tissues and correlated with patient prognosis. In vitro, TNBC cell lines were modified to knock down or overexpress GPR173 and GnRHR. Cell proliferation, migration, invasion, and expression of dual specificity phosphatase 1 (DUSP1), phosphorylated/total protein kinase B (AKT), phosphorylated/total extracellular signal-regulated kinase (ERK), and matrix metallopeptidase 2 (MMP2) were evaluated.

Results: GPR173 and GnRHR expression was significantly reduced in TNBC tumors compared to normal breast tissues. Low expression of either protein correlated with poorer overall survival and increased lymph node metastasis. In vitro, GPR173 knockdown promoted TNBC cell proliferation, migration, and invasion, and reduced GnRHR expression. These changes were accompanied by increased phosphorylation of AKT and ERK, and elevated MMP2 expression. Notably, the pro-proliferative, pro-migratory, and pro-invasive effects of GPR173 knockdown were reversed by rescue overexpression of GnRHR. This GnRHR overexpression was accompanied by upregulation of DUSP1, dephosphorylation of AKT and ERK, and decreased MMP2 levels.

Conclusions: Based on these in vitro data, GPR173 likely constrains the pro-proliferative, pro-migratory, and pro-invasive phenotypes of TNBC cells by enhancing GnRHR signaling. These findings highlight GnRHR and GPR173 as potential therapeutic targets for TNBC.

Accumulating evidence demonstrates that the tumor microenvironment (TME) drives immune suppression through complicated regulations including host-microbe interactions, which poses vaginal microbiome as one of vital regulators of immune microenvironment. This narrative review examined the composition and dynamic changes of vaginal microbiota during carcinogenesis, focusing on mechanistic insights linking microbial dysbiosis to tumor immunity. Notably, commensal bacteria exhibit diverse immunoregulatory functions that can either potentiate or inhibit anti-tumor responses. Clinical evidence further reveals that CST IV microbiota associates with significantly elevated cancer risk, while probiotic interventions show promise in restoring immune surveillance. Critical gaps in standardization of microbiota-based therapies are addressed, emphasizing the need for strain-specific characterization and optimized delivery systems. Collectively, deciphering vaginal microbiome-immune crosstalk opens new avenues for precision interception against cervical cancer.

Background: Artificial intelligence (AI) is increasingly applied to colposcopy to enhance the detection of cervical intraepithelial neoplasia (CIN) and cervical cancer. We conducted a systematic review to summarize the diagnostic performance achieved by AI‑based colposcopic systems.

Methods: Following the PRISMA 2020 guidelines, the PubMed database was searched using the search terms 'artificial intelligence' and 'colposcop*' for articles published between 2019 and 2024. From the initial 43 articles retrieved, 19 studies were selected based on specific inclusion criteria: original research articles, written in the English language, and relevant to CIN or cervical cancer diagnosis. For each, we extracted the sample size, AI architecture (e.g., convolutional neural networks, U-Net/DeepLab V3 + segmentation models, multimodal fusion networks), reference standard, and reported metrics (sensitivity, specificity, accuracy, and area under the curve).

Results: Across multiple studies, AI systems demonstrated superior diagnostic accuracy, sensitivity, and specificity, particularly for early detection of high-risk lesions and classification of cervical abnormalities. Deep-learning models, such as convolutional neural networks, consistently outperformed conventional methods by reducing diagnostic variability and offering robust performance even in low-resource settings. The review also highlights the potential of AI for real-time diagnostics and its capacity to support clinical decision-making via automated systems.

Conclusion: AI has the potential to revolutionize cervical cancer diagnosis and management by enhancing the accuracy and efficiency of colposcopic evaluations. However, challenges remain, including the development of standardized datasets, validation in diverse populations, and ethical considerations surrounding data privacy and access to technology. Continued research and development are crucial to harness AI's global potential to improve patient outcomes.

Background: With the increasing number of cancer survivors, second primary malignancies (SPMs) are attracting clinical interest. Although SPMs following multiple myeloma (MM) have been studied, data on second primary multiple myeloma (SPMM) remain limited. This study aimed to compare the clinical characteristics and outcomes of SPMM with those of primary MM through a retrospective analysis.

Methods: We retrospectively reviewed 183 patients with primary MM and 12 patients with SPMM treated at a single center between 2003 and 2022. To reduce selection bias, propensity score matching (1:3) was performed based on age, sex, year of MM diagnosis, and International Staging System stage. Survival outcomes were assessed using Kaplan-Meier analysis and Cox proportional hazards models.

Results: After matching, 48 patients (36 with primary MM and 12 with SPMM) were included in the final analysis. At the time of MM diagnosis, 83.3% of patients with SPMM had achieved complete remission of their primary malignancy. All but one received standard MM treatment. The median overall survival (OS) was 45.1 months for the primary MM group and 41.5 months for the SPMM group. There was no statistically significant difference in OS between the groups (hazard ratio: 0.72; 95% confidence interval: 0.33-1.56).

Conclusions: Patients with SPMM, most of whom had well-controlled primary cancers, received active treatment and demonstrated clinical outcomes not significantly different from those with primary MM. These findings support the use of aggressive treatment strategies for SPMM. Larger prospective studies are warranted to establish optimal treatment strategies.

Background: This retrospective cohort study aims to study the changes of the exposed volume of the bladder and rectum under different filling states, and to clarify the influences of the morphing organs on themselves and each other, to provide the basis for reducing the risk of organ damage by intensity-modulated radiotherapy (IMRT) for cervical cancer.

Methods: A retrospective analysis was performed on 24 patients with cervical cancer who received IMRT. Before radiotherapy, a comfortably full bladder and active defecation was ensured for all patients, and interative cone-beam computed tomography (iCBCT) was performed to delineate the bladder, rectum, and small intestine. The filling degree of the bladder, rectum, and small intestine and their intersection with the planned target volume were recorded.

Results: 83.44% of patients exhibited reduced bladder volume during treatment. When the planned bladder volume was 400-500 cc, the bladder volume changed the least during treatment (F = 58.39, P < .001). The exposed volume of the small intestine was moderately correlated with the degree of bladder filling (r = -.674, P < .01). For every 10% increase in bladder volume, the exposed volume of the small intestine decreased by 24.05% (P < .01). Furthermore, 45.83% patients had an increase in rectum volume during treatment. The exposed volume increased by 9.47% for every 10% increase in rectum volume (P < .01).

Conclusion: Comfortable bladder and active defecation regimens may not keep bladder and rectal stability. Targeting a planned bladder volume of 400 to 500cc minimizes intrafraction variability. Strategic bladder filling optimization may mitigate small intestine exposure.

Background: Gastric cancer remains a leading cause of cancer-related death. Early detection is crucial, but effective non-invasive screening methods are lacking. This study investigates the diagnostic potential of salivary Cystatin S (CST4) and MicroRNA-223 (miR-223) biomarkers, integrated with health-related factors for early gastric cancer detection.

Methods: Forty-five patients with gastric cancer and 45 healthy controls participated in this case-control study. Saliva samples were collected and analyzed for CST4 and miR-223 levels. Demographic data and health-related factors, including hot drink consumption, gastric ulcer history, Helicobacter pylori infection, body mass index (BMI), DMFT (Dental Decay, Missing, and Filled Teeth), and salty food intake, were also collected through a standardized questionnaire. Salivary CST4 levels were determined using enzyme-linked immunosorbent assay (ELISA), and miR-223 levels were quantified using real-time polymerase chain reaction (PCR). Statistical analyses, encompassing multiple logistic regression, were conducted to evaluate the diagnostic efficacy of the biomarkers alongside health-related parameters.

Results: Significant differences in salivary CST4 and miR-223 levels were observed between gastric cancer patients and healthy controls (P < 0.001). Combining salivary biomarkers and health-related factors yielded high accuracy, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.89 for the model using CST4 and miR-223. Multiple logistic regression analysis identified several health-related factors, including gastric ulcer history and Helicobacter pylori infection, as significant predictors of gastric cancer risk. The inclusion of health factors, along with biomarkers, enhanced early detection's sensitivity and specificity.

Conclusions: The study highlights the potential of salivary biomarkers CST4 and miR-223 as non-invasive tools for early gastric cancer detection. Integrating these biomarkers with health-related factors, such as gastric ulcer history and Helicobacter pylori infection, enhances the risk assessment and diagnostic accuracy for gastric cancer.

Background: Accurate intraoperative navigation remains challenging in gastrointestinal tumor surgery. This study aims to explore the potential of optical coherence tomography (OCT) and endoscopic ultrasonography (EUS) in enhancing the accuracy of intraoperative navigation.

Methods: This single-center diagnostic study was conducted at Northern Jiangsu People's Hospital from August to December 2024. This study is part of a prospective study, and more patients will be recruited in the future. The normal tissues, tumor tissues, vascular tissues, adipose tissues and lymph nodes of 12 patients with gastrointestinal tumors were collected for OCT and EUS scanning, and the image differences were compared. In addition, 43 lymph node specimens from 18 randomly selected patients were scanned by OCT and EUS, and pathological reports were used as the baseline. The results of OCT and EUS were compared retrospectively.

Results: There are notable differences between OCT and EUS imaging. EUS can capture images of the entire tissue layer, making it more effective than OCT in assessing tumor invasion depth. Conversely, OCT serves as an "optical biopsy," providing higher precision in the early stages of lesions. Our further research indicates that the combined application of these modalities holds significant potential. In a double-blind evaluation of 43 lymph nodes from 18 randomly selected patients, OCT demonstrated a sensitivity of 81.25%, specificity of 88.89%, and a positive predictive value (PPV) of 81.25%. In comparison, EUS showed a sensitivity of 87.50%, specificity of 85.19%, and a PPV of 77.78%. The combined use of OCT and EUS achieved a sensitivity of 93.75%, specificity of 92.59%, and a PPV of 88.24%.

Conclusions: The combined use of OCT and EUS can enhance sensitivity and specificity, thereby improving the accuracy of intraoperative navigation.

Trial registration: Chinese Clinical Trial Registry (No. ChiCTR2400088875); Registered 28 August 2024, first patient enrolled 20 September 2024.

Background: In non-small cell lung cancer (NSCLC) treatment, immunotherapy has become the standard therapy when platinum-based chemotherapy is ineffective, in the absence of a targetable mutation. However, a significant proportion of patients do not benefit from this treatment, underscoring the critical need for predictive biomarkers. This study aims to investigate the potential predictive role of immature granulocytes in response to nivolumab treatment, which can be used as a second-line therapy independent of programmed death ligand 1 (PDL-1) expression and other markers. Furthermore, the study seeks to determine whether there is a difference in the treatment response of immature granulocytes between the 2 main subtypes of NSCLC: lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD).

Methods: This retrospective study enrolled 50 patients with NSCLC who underwent treatment at the Kütahya Health Sciences University Evliya Çelebi Education and Research Hospital and Kütahya City Hospital between January 2021 and January 2025. The study examined the difference between patients' baseline immature granulocyte levels and their initial response to treatment, as assessed by positron emission tomography-computed tomography.

Results: The study found a statistically significant association between higher baseline immature granulocyte levels and poorer treatment response. Subgroup analysis by lung cancer subtype revealed that the difference was more prominent in the LUSCs group.

Conclusion: Immature granulocytes may predict response to nivolumab treatment in NSCLC patients, particularly in the LUSCs subgroup. Based on the findings of this study, immature granulocytes and other neutrophil-dependent inflammatory markers could serve as potential predictors of immunotherapy response and provide insights into the mechanisms of immunotherapy resistance, warranting further investigation. Our study may also encourage future research to look for separate markers for LUSCs and LUADs, given the continued critical need for predictive markers in this field.

Adrenocortical carcinoma is a rare, aggressive endocrine malignancy with limited effective systemic therapy options and an overall poor prognosis for unresectable or metastatic disease. Chemotherapy and mitotane are the traditional systemic therapies of choice. More recently, as drug development in oncology has shifted away from chemotherapy, a host of therapeutic approaches targeting novel mechanisms of action has been studied in adrenocortical carcinoma. This review summarizes all nonchemotherapeutic approaches that have been and/or are currently being tested in clinical trials for the treatment of unresectable or metastatic adrenocortical carcinoma.

Background: Multiple first-line chemotherapy-based combination regimens are available for patients with extensive-stage small cell lung cancer (ES-SCLC), however, direct head-to-head comparisons remain limited. This network meta-analysis (NMA) aimed to indirectly compare the efficacy and safety of various first-line combination therapies. Methods: A comprehensive literature search was conducted across electronic databases and academic conference proceedings to identify eligible randomized controlled trials (RCTs). Bayesian network meta-analysis and systematic review were performed on the selected studies. Primary outcomes included overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), along with adverse events of grade ⩾ 3 (grade ⩾ 3 AEs) and subgroup analyses. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022360249). Results: The analysis included 12 randomized trials encompassing 5840 patients and 14 treatment regimens. The combination of benmelstobart, anlotinib and chemotherapy showed the most significant improvement in PFS (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.26-0.41) and OS (HR = 0.61, 95% CI = 0.47-0.79) compared with chemotherapy alone. This regimen ranked highest for PFS (Bayesian ranking probability 99%) and OS (39%). However, it was also associated with a higher risk of Grade ⩾ 3 AEs (HR = 2.01, 95% CI = 1.09-3.73). In patients with baseline liver metastases, this regimen provided the greatest PFS benefit (99%), whereas serplulimab plus chemotherapy offered the best OS (53%). Conversely, for patients with baseline brain metastases, combination therapy failed to demonstrate a significant survival benefit. Conclusions: For treatment-naïve ES-SCLC patients, benmelstobart plus anlotinib plus chemotherapy yielded the most favorable outcomes in terms of PFS, OS and ORR, but a less favorable safety profile. These findings support its use as a potent therapeutic option in few patient populations.