Association of immune inflammatory biomarkers with pathological complete response and clinical prognosis in young breast cancer patients undergoing neoadjuvant chemotherapy.

Background: The persistence of inflammatory stimulus has a tight relationship with the development of age-related diseases, ultimately resulting in a gradual escalation in the prevalence of tumors, but this phenomenon is rare in young cancer patients. Breast cancer arising in young women is characterized by larger tumor diameters and more aggressive subtypes, so neoadjuvant chemotherapy (NACT) can be especially appropriate for this population. Immune inflammatory biomarkers have been reportedly linked to the prognosis of some malignant tumor types, with varying results. In this study, we investigated the possible predictive value of blood-based markers in young breast cancer patients undergoing NACT, in addition to the association between the clinicopathological features and prognosis. Methods: From December 2011 to October 2018, a total of 215 young breast cancer patients referred to Harbin Medical University Cancer Hospital received NACT and surgery were registered in this retrospective study. The pretreatment complete blood counts were used to calculate the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV). Results: NLR, PLR, MLR, and PIV optimal cut-off values were 1.55, 130.66, 0.24, and 243.19, as determined by receiver operating characteristic analysis. Multivariate analysis revealed that PIV, HR status, HER-2 status, and Ki-67 index were all independent predictive factors for pathological complete response. Subgroup analysis revealed that young breast cancer patients in the population characterized by low PIV and HR negative group were more likely to get pCR (P=0.001). The five-year overall survival (OS) rate was 87.9%, and Cox regression models identified PIV as independently related to OS. Conclusion: In the present study, the pretreatment PIV was found to be a useful prognostic indicator for pCR and long-term survival in young breast cancer patients undergoing NACT. High immune and inflammation levels, MLR and PIV were connected to poor clinical prognosis in young breast cancer patients. PIV is a promising biomarker to guide strategic decisions in treating young breast cancer.

Estrogen receptor-negative/progesterone receptor-positive breast cancer has distinct characteristics and pathologic complete response rate after neoadjuvant chemotherapy.

PURPOSE: The status of hormone receptors (HR) is an independent factor affecting survival and chemotherapy sensitivity in breast cancer (BC) patients, with estrogen receptor (ER) and progesterone receptor (PR) having the most significant effects. The ER-/PR + phenotype has been controversial in BC, and experts will face many challenges in determining treatment strategies. Herein, we systematically analyzed the clinicopathological characteristics of the ER-/PR + phenotype in BC patients and the response to chemotherapy. PATIENTS AND METHODS: We included two cohorts. The first cohort counted the relationship between clinicopathologic data and survival outcomes for 72,666 female patients in the Surveillance, Epidemiology, and End Results (SEER) database. The second cohort analyzed the relationship between clinicopathological data and pathologic complete response (pCR) rate in 879 patients at the Harbin Medical University Cancer Hospital. The classification data were compared by the chi-square test and Fister's exact test of the Logistic regression model, and predictor variables with P < 0.05 in the univariate analysis were included in the multivariate regression analysis. The Kaplan-Meier method evaluated breast cancer-specific survival (BCSS) and overall survival (OS) to investigate the relationship between different HR typing and survival and pCR. RESULTS: In the two cohorts, 704 (0.9%) and 11 (1.3%) patients had the ER-/PR + phenotype, respectively. The clinicopathologic features of patients with the ER-/PR + phenotype are more similar to those of the ER-/PR- phenotype. The ER-/PR + phenotype is more common in younger and premenopausal women, and most ER-/PR + phenotypes exhibit higher histological grades. Survival analysis showed that there were significant differences in OS and BCSS among patients with different HR states (P < 0.001). The survival results of patients with the ER + /PR + phenotype were the best. The prognosis of the ER-/PR + phenotype was similar to that of the ER-/PR- phenotype. On the other hand, we found that HR status was also an independent predictor of post-NAC pCR rate in BC patients. The ER + /PR- and ER-/PR- phenotypes were more sensitive to chemotherapy than the ER + /PR + phenotypes. CONCLUSION: HR status is the main factor affecting BC's survival outcome and pCR rate. Patients with the ER-/PR + phenotype possess more aggressive biological factors and can benefit significantly from chemotherapy. We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical treatment.

Correlation between second and first primary cancer: systematic review and meta-analysis of 9 million cancer patients.

BACKGROUND: Many survivors of a first primary cancer (FPCs) are at risk of developing a second primary cancer (SPC), with effects on patient prognosis. Primary cancers have different frequencies of specific SPC development and the development of SPCs may be closely related to the FPC. The aim of this study was to explore possible correlations between SPCs and FPCs. METHODS: Relevant literature on SPCs was retrospectively searched and screened from four databases, namely, PubMed, EMBASE, Web of Science, and PMC. Data on the number of patients with SPC in 28 different organ sites were also collected from The Surveillance, Epidemiology, and End Results (SEER) 8 Registry and NHANES database. RESULTS: A total of 9 617 643 patients with an FPC and 677 430 patients with an SPC were included in the meta-analysis. Patients with a first primary gynaecological cancer and thyroid cancer frequently developed a second primary breast cancer and colorectal cancer. Moreover, those with a first primary head and neck cancer, anal cancer and oesophageal cancer developed a second primary lung cancer more frequently. A second primary lung cancer and prostate cancer was also common among patients with first primary bladder cancer and penile cancer. Patients with second primary bladder cancer accounted for 56% of first primary ureteral cancer patients with SPCs. CONCLUSIONS: This study recommends close clinical follow-up, monitoring and appropriate interventions in patients with relevant FPCs for better screening and early diagnosis of SPCs.

Electronic visualized double-lumen endobronchial tube for situs inversus totalis: A case report and literature review.

RATIONALE: Using an electronic visualized double-lumen endobronchial tube (E-visual DLT) allows for excellent surgical visualization during one-lung ventilation. Situs inversus totalis (SIT) is a rare autosomal recessive genetic condition wherein the bronchial and pulmonary lobar structures on the left and right sides of individuals are reversed compared to those of the general population. In the case of SIT, placing a left-sided E-visual DLT into the right bronchus might offer more advantageous one-lung ventilation. However, there have been no reported instances of using E-visual DLT single-lung ventilation anesthesia techniques for SIT. PATIENTS CONCERNS: We present a case report detailing the effective implementation of a visualized single-lung ventilation technique under general anesthesia in a 36-year-old male diagnosed with SIT. The patient had a mediastinal mass and underwent thoracoscopic resection of the mediastinal mass using a left-sided approach. DIAGNOSES: Based on the findings from the contrast-enhanced chest computed tomography (CT) results, the patient was diagnosed with SIT along with a mediastinal mass. Surgical intervention was proposed to alleviate the cardiac compression caused by the mass. Nevertheless, the administration and handling of anesthesia posed a notable challenge since clinical anesthesiologists encounter contradictory data and a limited number of evidence-based guidelines. INTERVENTIONS: Convened a multidisciplinary meeting prior to the initiation of anesthesia to formulate a comprehensive strategy. Throughout the anesthetic management, our team ensured meticulous monitoring, delivered sufficient oxygenation, and established hemodynamic equilibrium. The anesthesia team deliberated and devised a plan to employ a left-sided E-visual DLT placement through the right bronchus for right-sided one-lung ventilation in the patient with SIT. The process of anesthesia induction was subjected to repeated simulations to guarantee patient safety. OUTCOMES: Due to the meticulous and effective administration and supervision of anesthesia, the surgery was completed as planned. Subsequently, the removal of the E-visual DLT was executed without any complications. LESSONS: Data and literature about SIT are scarce, necessitating thorough pre-planning and preparation.

Vacuum-assisted biopsy system for breast lesions: a potential therapeutic approach.

Purpose: The primary objective is to optimize the population eligible for Mammotome Minimally Invasive Surgery (MIS) by refining selection criteria. This involves maximizing procedure benefits, minimizing malignancy risk, and reducing the rate of malignant outcomes. Patients and methods: A total of 1158 female patients who came to our hospital from November 2016 to August 2021 for the Mammotome MIS were analyzed retrospectively. Following χ2 tests to screen for risk variables, binary logistic regression analysis was used to determine the independent predictors of malignant lesions. In addition, the correlation between age and lesion diameter was investigated for BI-RADS ultrasound (US) category 4a lesions in order to better understand the relationship between these variables. Results: The malignancy rates of BI-RADS US category 3, category 4a and category 4b patients who underwent the Mammotome MIS were 0.6% (9/1562), 6.4% (37/578) and 8.3% (2/24) respectively. Malignant lesions were more common in patients over the age of 40, have visible blood supply, and BI-RADS category 4 of mammography. In BI-RADS US category 4a lesions, the diameter of malignant tumor was highly correlated with age, and this correlation was strengthened in patients over the age of 40 and with BI-RADS category 4 of mammography. Conclusion: The results of this study demonstrate that the clinical data and imaging results, particularly age, blood supply, and mammography classification, offer valuable insights to optimize patients' surgical options and decrease the incidence of malignant outcomes.

Clinical characteristics and pathologic complete response (pCR) rate after neoadjuvant chemotherapy in postpartum women with breast cancer.

PURPOSE: Breast cancer (BC) is currently the leading cause of death in women worldwide. Studies have confirmed that pregnancy is an independent factor affecting the survival of BC patients. BC found during pregnancy, lactation, or shortly after delivery is what we used to think of as pregnancy-associated breast cancer (PABC). The current expert definition of this concept is not uniform; however, there is growing evidence that postpartum breast cancer (PPBC) differs from other types of BC in terms of both biological features and prognosis, with a slightly different focus on diagnosis and treatment. With the increase of female reproductive age population and changes in fertility policies in China, patients with PPBC are receiving increasing attention. Here, we systematically analyzed the clinicopathological characteristics and chemotherapeutic response of patients with PPBC. We retrospectively analyzed the clinicopathological data, molecular subtypes, chemotherapy regimens, and pathological complete remission (pCR) rates of 1343 patients with non-metastatic BC at Harbin Medical University Cancer Hospital from January 1, 2012 to May 31, 2023. The categorical data were compared by chi-square test and Fisher exact test using logistic regression model. Predictor variables with P < 0.05 in the univariate analysis were included in the multivariate regression analysis to investigate the relationship between different age groups and pCR. RESULTS: A total of 714 patients were eligible for analysis in this study, and 667 patients had a history of pregnancy, 40 (5.6%) of whom were PPBC patients. When diagnosed with BC, patients with PPBC were younger, more likely to undergo breast-conserving surgery (BCS), and more likely to achieve pCR (P < 0.05). In molecular typing, human epidermal growth factor receptor 2 (HER-2)-positive and triple-negative breast cancer (TNBC) were more frequent. In the entire cohort, HER-2 expression and delivery status were independent predictors of pCR rates in BC patients after neoadjuvant chemotherapy (NAC). CONCLUSION: Our findings suggest that postpartum status is an independent predictor of pCR attainment in BC patients. PPBC is more sensitive to chemotherapy than other patients.We need to pay more attention to this group and achieve individualized treatment, which will help us treat BC better and provide new targets and blueprints for our clinical therapy.

Catalyst-free thiazolidine formation chemistry enables the facile construction of peptide/protein-cell conjugates (PCCs) at physiological pH.

Although numerous genetic, chemical, and physical strategies have been developed to remodel the cell surface landscape for basic research and the development of live cell-based therapeutics, new chemical modification strategies capable of decorating cells with various genetically/non-genetically encodable molecules are still urgently needed. Herein, we describe a remarkably simple and robust chemical strategy for cell surface modifications by revisiting the classical thiazolidine formation chemistry. Cell surfaces harbouring aldehydes can be chemoselectively conjugated with molecules containing a 1,2-aminothiol moiety at physiological pH without the need to use any toxic catalysts and complicated chemical synthesis. Through the combined use of thiazolidine formation and the SpyCatcher-SpyTag system, we have further developed a SpyCatcher-SpyTag Chemistry Assisted Cell Surface Engineering (SpyCASE) platform, providing a modular approach for the construction of large protein-cell conjugates (PCCs) in their native state. Thiazolidine-bridged molecules can also be detached from the surface again through a biocompatible Pd-catalyzed bond scission reaction, enabling reversible modification of living cell surfaces. In addition, this approach allows us to modulate specific cell-cell interactions and generate NK cell-based PCCs to selectively target/kill several EGFR-positive cancer cells in vitro. Overall, this study provides an underappreciated but useful chemical tool to decorate cells with tailor-made functionalities.

Chemical and Biological Strategies for Profiling Protein-Protein Interactions in Living Cells.

Protein-protein interactions (PPIs) play critical roles in almost all cellular signal transduction events. Characterization of PPIs without interfering with the functions of intact cells is very important for basic biology study and drug developments. However, the ability to profile PPIs especially those weak/transient interactions in their native states remains quite challenging. To this end, many endeavors are being made in developing new methods with high efficiency and strong operability. By coupling with advanced fluorescent microscopy and mass spectroscopy techniques, these strategies not only allow us to visualize the subcellular locations and monitor the functions of protein of interest (POI) in real time, but also enable the profiling and identification of potential unknown interacting partners in high-throughput manner, which greatly facilitates the elucidation of molecular mechanisms underlying numerous pathophysiological processes. In this review, we will summarize the typical methods for PPIs identification in living cells and their principles, advantages and limitations will also be discussed in detail.

Randomized Trial of First-Line Tyrosine Kinase Inhibitor With or Without Radiotherapy for Synchronous Oligometastatic EGFR-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Adding radiotherapy (RT) to systemic therapy improves progression-free survival (PFS) and overall survival (OS) in oligometastatic non-small cell lung cancer (NSCLC). Whether these findings translate to epidermal growth factor receptor (EGFR)-mutated NSCLC remains unknown. The SINDAS trial (NCT02893332) evaluated first-line tyrosine kinase inhibitor (TKI) therapy for EGFR-mutated synchronous oligometastatic NSCLC and randomized to upfront RT vs no RT; we now report the prespecified interim analysis at 68% accrual. METHODS: Inclusion criteria were biopsy-proven EGFR-mutated adenocarcinoma (per amplification refractory mutation system or next generation sequencing), with synchronous (newly diagnosed, treatment naïve) oligometastatic (≤5 metastases; ≤2 lesions in any one organ) NSCLC without brain metastases. All patients received a first-generation TKI (gefitinib, erlotinib, or icotinib), and randomization was between no RT vs RT (25-40 Gy in 5 fractions depending on tumor size and location) to all metastases and the primary tumor/involved regional lymphatics. The primary endpoint (intention to treat) was PFS. Secondary endpoints included OS and toxicities. All statistical tests were 2-sided. RESULTS: A total of 133 patients (n = 65 TKI only, n = 68 TKI with RT) were enrolled (2016-2019). The median follow-up was 23.6 months. The respective median PFS was 12.5 months vs 20.2 months (P < .001), and the median OS was 17.4 months vs 25.5 months (P < .001) for TKI only vs TKI with RT. Treatment yielded no grade 5 events and a 6% rate of symptomatic grade 3-4 pneumonitis in the TKI with RT arm. Based on the efficacy results of this prespecified interim analysis, the ethics committee recommended premature cessation of this trial. CONCLUSIONS: As compared with a first-line TKI alone, addition of upfront local therapy using RT statistically significantly improved PFS and OS for EGFR-mutated NSCLC.

High-Quality Genome Resource of Gilbertella persicaria Causing Peach Soft Rot.

Peach soft rot caused by Gilbertella persicaria is an economically important disease. Here, we report a high-quality complete and annotated genome sequence of G. persicaria strain TFLB-J, isolated from peach fruit in Yuanyang county of Henan Province, China. The assembly consists of 91 scaffolds with an estimated genome size of 33.59 Mb and N50 length of 0.92 Mb, encoding 13,296 predicted protein-coding genes. The whole-genome sequence could provide gene resources for further study of pathogenic effectors and comparative genomics of peach soft rot pathogens.

Extensive prediction of drug response in mutation-subtype-specific LUAD with machine learning approach.

Background: Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death worldwide. Therapeutic failure in lung cancer (LUAD) is heavily influenced by drug resistance. This challenge stems from the diverse cell populations within the tumor, each having unique genetic, epigenetic, and phenotypic profiles. Such variations lead to varied therapeutic responses, thereby contributing to tumor relapse and disease progression. Methods: The Genomics of Drug Sensitivity in Cancer (GDSC) database was used in this investigation to obtain the mRNA expression dataset, genomic mutation profile, and drug sensitivity information of NSCLS. Machine Learning (ML) methods, including Random Forest (RF), Artificial Neurol Network (ANN), and Support Vector Machine (SVM), were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical methods. The most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods, and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer subtype. Finally, the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available datasets. Results: Our analyses yielded 1,564 gene features and 45 mutational features for 46 drugs. Applying the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response (area under the curve [AUC] 0.875) using CIT, GAS2L3, STAG3L3, ATP2B4-mut, and IL15RA-mut as molecular features. Furthermore, the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance (AUC 0.780) in Gefitinib with CCL23-mut. Conclusion: This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.

Breast Cancer Exosome-Derived miR-425-5p Induces Cancer-Associated Fibroblast-Like Properties in Human Mammary Fibroblasts by TGFß1/ROS Signaling Pathway.

The connection between the cellular microenvironment and tumor cells is crucial for tumor progression. However, the process by which normal fibroblasts (NFs) become cancer-associated fibroblasts (CAFs) is unknown, and mounting evidence suggests that some microRNAs (miRNAs) have an important role in converting NFs into CAFs. Breast cancer (BC) has been proven to have enhanced miR-425-5p expression in order to support progression. We discovered that human mammary fibroblasts (HMFs) could uptake BC cell line-derived exosomes to change their properties, promoting the switch to the CAF phenotype and increasing cell motility, as evidenced by an increase in CAF activation-related marker protein expression and cell proliferation, invasion, and migration. Transfection of exosomes is obtained from BC cells, and miR-425-5p inhibitors suppressed the aforementioned effects as well as lowered chemokine levels and gene expression related with proliferation and metastasis. By suppressing the expression of its target gene TGFßRII (TGFß1 receptor), miR-425-5p enhanced the transition of HMFs to the CAF phenotype. MDA-MB-231 cells and CAFs stimulated by HMF absorption of MDA-MB-23-derived exosomes showed similar proliferation, invasion, migration, and expression of -SMA, FAP, CXCL1, IL-6, TGFß1, P21, P27, Ki67, vimentin, E-cadherin, N-cadherin, α-catenin, fibronectin, and MMP-2. TGFß1 overexpression enhanced ROS production. Finally, we found that HMFs transiently transfected with miR-425-5p can promote tumor growth in vivo. Finally, these findings provide fresh insight on miR-425-5p as an important mediator of the interaction between BC cells and stroma.

Prognostic value of Beclin 1, EGFR and ALK in non-squamous non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The study was carried out to investigate the prognostic value of Beclin 1, EGFR and ALK for this cancer. Patients diagnosed with non-squamous NSCLC and admitted to our hospital from January 2011 to September 2016 were analyzed. Expression of Beclin 1 and mutation of EGFR and ALK were assessed using polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) and analyzed for their relationship with demographic and clinical characteristics of the patients. Multivariate Cox regression models were applied to analyze the risk factors associated with survival and receiver response curves (ROC) were plotted to determine the prognostic value of Beclin 1, EGFR and ALK for patients with non-squamous NSCLC. Compared with adjacent normal tissue, Beclin 1 expression was elevated in the cancer tissue significantly; assessments of EGFR and ALK mutations showed that out of the 480 patients, 233 (48.5%) and 75 (12.6%) patients had EGFR and ALK mutations. Univariate analysis revealed that Beclin 1 level, EGFR and ALK mutations were associated with lymph node metastasis, TNM stage, tumor differentiation and prognosis, but not with gender, age and smoking status. The Kaplan-Meier survival analysis indicated that low Beclin 1 expression and positive EGFR and ALK rearrangements were associated with higher survival rate and longer progress-free survival (PFS). Multivariate Cox regression analysis showed that Beclin 1, EGFR, ALK mutations, tumor differentiation grade, TNM stage and lymph node metastasis were independently associated with PFS. ROC analysis showed that Beclin 1, EGFR and ALK were significant predictors for PFS; the areas under curve (AUC) for Beclin 1, EGFR and ALK were 0.812 (P = 0.018, cut-off value: 1.2), 0.781 (P = 0.011, cut-off value: 15%) and 0.722 (P = 0.010, cut-off value: 11%), respectively, suggesting that they have significant prognostic value for lung cancer patients. Our data indicate that Beclin 1, EGFR and ALK genes are associated with the prognosis of patients with non-squamous NSCLC. High Beclin 1 expression and negative EGFR and ALK mutations predict a poor prognosis with PFS.

Lumican is elevated in the lung in human and experimental acute respiratory distress syndrome and promotes early fibrotic responses to lung injury.

BACKGROUND: Fibroproliferative repair starts early in the inflammatory phase of acute respiratory distress syndrome (ARDS) and indicates a poor prognosis. Lumican, a small leucine-rich proteoglycan, is implicated in homeostasis and fibrogenesis, but its role in ARDS is unclear. METHODS: Bronchoalveolar lavage fluid (BALF) samples were obtained from ARDS patients (n = 55) enrolled within 24 h of diagnosis and mechanically ventilated (n = 20) and spontaneously breathing (n = 29) control subjects. Lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse models were intratracheally administered an adeno-associated virus (AAV) vector expressing lumican shRNA. Primary human lung fibroblasts (HLF) and small airway epithelial cells (SAECs) were cultured with tumour necrosis factor (TNF)-α or lumican. Luminex/ELISA, histochemistry/immunohistochemistry, immunofluorescence microscopy, quantitative real-time PCR, and western blotting were performed. RESULTS: Lumican levels were significantly higher in the BALF of ARDS patients than in that of ventilated or spontaneously breathing controls (both p < 0.0001); they were correlated with the PaO2/FiO2 ratio and levels of proinflammatory cytokines (interleukin-6, interleukin-8, and TNF-α) and profibrotic factors (fibronectin, alpha-1 type I collagen [COL1A1], and alpha-1 type III collagen [COL3A1]). Lumican expression was enhanced in the alveolar walls and airway epithelium in the ALI mouse model. Murine lumican levels were also linked to proinflammatory and profibrotic cytokine levels in the BALF. In vitro, TNF-α induced the synthesis and secretion of lumican in HLF. In turn, lumican increased the expression of alpha-smooth muscle actin (α-SMA), COL1A1, and COL3A1 in HLF, upregulated α-SMA and COL3A1, downregulated E-cadherin, and caused spindle-shaped morphological changes in SAECs. Moreover, increased ERK phosphorylation and Slug were noted in both HLF and SAECs treated with lumican. In vivo, AAV-mediated knockdown of lumican inhibited the pulmonary production of fibronectin and COL3A1 and alleviated lung fibrotic lesions in LPS-challenged mice. CONCLUSIONS: Pulmonary lumican levels were increased early in human and experimental ARDS and linked to disease severity and inflammatory fibrotic processes. Lumican triggers the transdifferentiation of lung fibroblasts into myofibroblasts and epithelial-mesenchymal transition in SAECs, possibly via the ERK/Slug pathway. Knockdown of pulmonary lumican attenuated extracellular matrix deposition in ALI mice. Overall, lumican promotes fibrotic responses in the early phase of ARDS, suggesting its potential as a therapeutic target.

Longitudinal Association of Universal Screening and Treatment for Major Depressive Disorder with Survival in Cancer Patients.

Evidence for clinical screening and intervention for depression in cancer and the effect of this intervention on cancer prognosis is suboptimal. This study substantialized a complete model with universal screening and intervention for major depressive disorder (MDD) and explored its effect on survival in patients. This longitudinal study recruited cancer patients routinely screened for MDD with a two-stage model. Data including sex, age, cancer diagnosis, first diagnosis date, date of death, cancer stage, and MDD diagnosis and treatment were collected from medical records and the national registration system for cancer. Kaplan−Meier's survival analysis and the Cox proportional hazards regression model were applied to analyze the effects of associated factors on survival. Further subgroup analysis for 14 types of cancer primary site was also performed. Overall, the hazard for patients adhering to psychiatric treatment for MDD before cancer diagnosis was not statistically different from that for patients without MDD (hazard ratio (HR) = 1.061, 95% CI: 0.889−1.267, p = 0.512). The hazard for patients adhering to psychiatric treatment after cancer diagnosis was significantly lower than that for patients without MDD (HR = 0.702, 95% CI: 0.607−0.812, p < 0.001). Those who were diagnosed with MDD after cancer diagnosis and adhered poorly to psychiatric treatment had the greatest hazard (HR = 1.829, 95% CI: 1.687−1.984, p < 0.001). The effect of intervention for MDD varied across different primary cancer types.

Establishing an 8-gene immune prognostic model based on TP53 status for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) results in a majority of cancer burden worldwide. TP53 is the most commonly mutated in LUAD. This study aimed to reveal the relation between TP53 and tumor microenvironment (TME) for improving LUAD treatment. METHODS: Differentially expressed genes (DEGs) related to immunity were analyzed between TP53-WT and TP53-MUT groups. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to screen prognostic DEGs. Two independent datasets were included to evaluate the robustness of the prognostic model. RESULTS: An 8-gene prognostic model containing ANLN, CCNB1, DLGAP5, FAM83A, GJB2, NAPSA, SFTPB, and SLC2A1 was established based on DEGs. LUAD samples were classified into high- and low-risk groups with differential overall survival in the two datasets. M0 macrophages, M1 macrophages, and activated memory CD4 T cells were more enriched in high-risk group. Immune checkpoints of PDCD1, LAG3, and CD274 were also high-expressed in high-risk group. CONCLUSION: The study improved the understanding of the role of TP53 in the TME modulation. The 8-gene model had robust performance to predict LUAD prognosis in clinical practice. In addition, the eight prognostic genes may also serve as potential targets for designing therapeutic drugs for LUAD patients.

Memantine ameliorates oxaliplatin-induced neurotoxicity via mitochondrial protection.

Oxaliplatin is an effective chemotherapeutic agent for the treatment of malignant tumors. However, severe oxaliplatin-induced neurotoxicity has been well documented. Memantine is a drug for the management of Alzheimer's Disease (AD) due to its promising neuroprotective properties. We hypothesize that Memantine possesses a beneficial role against chemotherapy-induced neuronal damages. In this study, we established an oxaliplatin-induced neurotoxicity assay model in human SHSY-5Y neuronal cells and investigated the protective effect of Memantine. We showed that Memantine treatment ameliorated oxaliplatin-elevated intracellular production of reactive oxygen species (ROS), lipid product malondialdehyde (MDA), and NOX-2 expression. Memantine alleviated impairment of the mitochondrial membrane potential and ATP production by oxaliplatin. As a result, Memantine showed a protective role against oxaliplatin-induced cytotoxicity. Moreover, the terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) apoptosis assay revealed that Memantine protected oxaliplatin-induced apoptosis through mitigating the ratio of Bax/Bcl-2 and Caspase-3 cleavage. We concluded Memantine ameliorated the neurotoxicity of oxaliplatin in a mitochondrial-dependent pathway.

Rapid identification of tumor-reactive T-cell receptors by RNA preamplification-based single-cell sequencing.

T-cell receptor (TCR)-transduced T (TCR-T) cell therapy has shown promising efficacy in the clinical treatment of malignant cancers. However, the populations covered by reported TCRs are still limited. Tumor infiltrating lymphocytes (TILs) are natural reservoirs of tumor-reactive T cells and TCRs. Approaches are required for the fast and cost-effective identification of tumor-reactive TCRs from TILs. The widely employed TCR identification approaches by the clonal expansion of TILs involve a TCR singularization process for the direct pairing of TCR Vα and the Vß chain. However, the clonal expansion of T cells is well known to require extensive time and effort due to the involvement of T cell cultures. Several single-cell multiplexing PCR methods followed by Sanger sequencing have been developed, representing a cost-effective and fast approach for single-cell TCR identification. In this study, an RNA-based preamplification step was included in the single-cell TCR sequencing, which can reduce the multiplexing PCR amplification to one round. Moreover, the cDNA product of RNA preamplification is derived from the whole genome mRNA, instead of TCR mRNA only by multiplexing primers-based DNA preamplification, which is valuable for many other analyses (e.g., phenotypic analysis) of the tumor-reactive T cells that can be correlated with the identified TCRs. The feasibility for both single α chain and dual α chain TILs of this approach highlights its potential value as a rapid and cost-effective sequencing strategy for the development of TCR-T therapies for solid cancers.

Prognostic Factors of IIIAN2 Non-Small-Cell Lung Cancer after Complete Resection: A Systemic Review and Meta-analysis.

METHODS: An extensive data search was conducted from all leading databases including PubMed, Google Scholar, Embase, and Cochrane. Fifteen studies were selected according to the PRISMA model of data selected to conduct this systemic review meta-analysis. RESULTS: Total 4444 patients were evaluated among fifteen selected studies. A number of lymph nodes involved (n = 3965), level of lymph nodes (n = 3422), and complete tumor resection (n = 3255) were the most reported prognostic factors. CONCLUSION: This study exhibits the overall significance of all prognostic factors of NSCLC IIIAN2 pathology for better patient management. However, other management strategies also play a significant contribution to achieving a better survival rate and less recurrence possibility.

Single-Cell Analysis Reveals Spatial Heterogeneity of Immune Cells in Lung Adenocarcinoma.

The impacts of the tumor microenvironment (TME) on tumor evolvability remain unclear. A challenge for nearly all cancer types is spatial heterogeneity, providing substrates for the emergence and evolvability of drug resistance and leading to unfavorable prognosis. Understanding TME heterogeneity among different tumor sites would provide deeper insights into personalized therapy. We found 9,992 cell profiles of the TME in human lung adenocarcinoma (LUAD) samples at a single-cell resolution. By comparing different tumor sites, we discovered high TME heterogeneity. Single-sample gene set enrichment analysis (ssGSEA) was utilized to explore functional differences between cell subpopulations and between the core, middle and edge of tumors. We identified 8 main cell types and 27 cell subtypes of T cells, B cells, fibroblasts and myeloid cells. We revealed CD4+ naive T cells in the tumor core that express high levels of immune checkpoint molecules and have a higher activity of immune-exhaustion signaling. CD8+ T cell subpopulations in the tumor core correlate with the upregulated activity of transforming growth factor-ß (TGF-ß) and fibroblast growth factor receptor (FGFR) signaling and downregulated T cell activity. B cell subtypes in the tumor core downregulate cytokine production. In this study, we revealed that there was immunological heterogeneity in the TME of patients with LUAD that have different ratios of immune cells and stromal cells, different functions, and various degrees of activation of immune-related pathways in different tumor parts. Therefore, clarifying the spatial heterogeneity of the tumor in the immune microenvironment can help clinicians design personalized treatments.