SLC4A4 is a novel driver of enzalutamide resistance in prostate cancer.

The androgen receptor signaling inhibitor (ARSI) enzalutamide (Enz) has shown critical efficacy in the treatment of advanced prostate cancer (PCa). However, the development of drug resistance is a significant factor contributing to mortality in PCa patients. We aimed to explore the key mechanisms of Enz-resistance. Through analysis of GEO databases, we identified SLC4A4 as a novel driver in Enz resistance. Long-term Enz treatment leads to the up-regulation of SLC4A4, which in turn mediates P53 lactylation via the NF-κB/STAT3/SLC4A4 axis, ultimately leading to the development of Enz resistance and progression of PCa. SLC4A4 knockdown overcomes Enz resistance both in vitro and in vivo. Hence, our results suggest that targeting SLC4A4 could be a promising therapeutic strategy for Enz resistance. STATEMENT OF SIGNIFICANCE: SLC4A4 is a novel driver of enzalutamide resistance.

Tislelizumab combined with GT chemotherapy for intimal sarcoma of inferior vena cava: A case report.

RATIONALE: Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods. PATIENT CONCERNS: A 54-year-old female patient presented to Fenghua District People's Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital. DIAGNOSES: The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG. INTERVENTIONS: The patient initially received GT chemotherapy (gemcitabine injection + docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation). OUTCOMES: The disease was stabilized after receiving the treatment. LESSONS: Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.

CRISPR genome-wide screening identifies PAK1 as a critical driver of ARSI cross-resistance in prostate cancer progression.

Next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide (Enza) and darolutamide (Daro), are initially effective for the treatment of advanced prostate cancer (PCa) and castration-resistant prostate cancer (CRPC). However, patients often relapse and develop cross-resistance, which consequently makes drug resistance an inevitable cause of CRPC-related mortality. By conducting a comprehensive analysis of GEO datasets, CRISPR genome-wide screening results, ATAC-seq data, and RNA-seq data, we systemically identified PAK1 as a significant contributor to ARSI cross-resistance due to the activation of the PAK1/RELA/hnRNPA1/AR-V7 axis. Inhibition of PAK1 followed by suppression of NF-κB pathways and AR-V7 expression effectively overcomes ARSI cross-resistance. Our findings indicate that PAK1 represents a promising therapeutic target gene for the treatment of ARSI cross-resistant PCa patients in the clinic. STATEMENT OF SIGNIFICANCE: PAK1 drives ARSI cross-resistance in prostate cancer progression.

Cause of death during nasopharyngeal carcinoma survivorship: a population-based analysis.

Background: Recently, the survival rate of nasopharyngeal carcinoma (NPC) patients has improved greatly due to developments in NPC treatments. But cause-specific mortality in NPC patients remains unclear. This study aims to investigate the common causes of death in NPC patients. Methods: Eligible patients with NPC were included from the Surveillance, Epidemiology, and End Results (SEER) database. Standardized mortality ratios(SMRs) were calculated to compare death rates in NPC patients with those in the general population. Results: A total of 3475 patients with NPC were included, of whom 1696 patients died during the follow-up period. 52.83% of deaths were caused by NPC, followed by other cancers (28.13%) and non-cancer causes (18.46%). The proportion of patients who died of NPC decreased over survival time. Moreover, non-cancer causes of death increase from 12.94% to 51.22% over time after 10 years of diagnosis. Heart diseases was the most common non-cancer cause of death in NPC patients. Conclusions: Although NPC remains the leading cause of death after NPC diagnosis, other non-NPC causes of death represent an increased number of death in NPC patients. These findings support the involvement of multidisciplinary care for follow-up strategy in NPC patients.

Evaluating the Role of Morphological Parameters in the Prostate Transition Zone in PHI-Based Predictive Models for Detecting Gray Zone Prostate Cancer.

Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P < .05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. Conclusion: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZ-adjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions.

Cone beam computed tomography indications for interdisciplinary therapy planning of impacted canines.

OBJECTIVE: To investigate how cone beam computed tomography (CBCT) affects the therapeutic planning of impacted maxillary canines. STUDY DESIGN: A total of 132 impacted canines from 89 pediatric patients were collected from 3 specialist clinics in Stockholm, Sweden. An interdisciplinary therapy planning team consisting of 5 dental specialists evaluated each case and chose their preferred treatment alternative, initially without and later with CBCT images, to decide whether CBCT was justified for therapy planning. Predefined variables measurable using only 2-dimensional (2D) assessments were analyzed using stepwise logistic regression analyses. RESULTS: The CBCT was considered indicated in 47% of the cases. Additional information from CBCT led to a treatment decision change in 9.8%. Significant 2D predictors for CBCT justification were horizontal canine angulation compared with vertical angulation (odds ratio [OR] = 10.9), extraction strategy involvement (OR = 6.7), and buccally positioned canines compared with palatal (OR = 5.3), central (OR = 25.0), and distal or uncertain positions (OR = 7.7). CONCLUSIONS: The benefit-risk assessment of CBCT for impacted canines may be reinforced by performing and applying justification decisions for CBCT acquisition at the therapeutic thinking level. If preliminary treatment planning motivates further in-depth investigation of either root status or tooth location, a CBCT is indicated.

The different prognostic factors between metastatic and nonmetastatic disease of esophageal neuroendocrine carcinoma.

PURPOSE: The specific risk factors of metastatic and nonmetastatic esophageal neuroendocrine carcinoma (NEC) are still uncertain. Whether primary site surgery is necessary for all patients with esophageal NEC is unknown. METHODS: Patients with esophageal NEC in the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2014 were selected. STATA 12 was used to analyze the clinical and pathological features of esophageal NEC. RESULTS: In total, 241 patients with esophageal NEC were included. Metastatic patients had shorter overall survival than nonmetastatic patients (6.03 versus 11.90 months, respectively). Prognostic factors varied between metastatic and nonmetastatic esophageal NEC. The location of the primary tumor is a key point for the prognosis of esophageal NEC. For nonmetastatic esophageal NEC, patients with tumors in the upper third of the esophagus had the worst survival, and patients with metastatic esophageal NEC with a primary tumor in the lower part of the esophagus tended to have an increased risk of death. Moreover, age ≥68 years (hazard ratio [HR] = 2.05; 95% confidence interval [CI]: 1.28-3.31; P < 0.01) and large cell carcinoma (HR = 2.79; 95% CI: 1.30-6.00; P < 0.01) were independent risk factors in patients with metastatic esophageal NEC. Primary site resection benefited patients with nonmetastatic esophageal NEC (HR = 0.20; 95% CI: 0.07-0.56; P < 0.01) rather than patients with metastatic esophageal NEC (HR = 0.91; 95% CI: 0.29-2.83; P > 0.05). CONCLUSIONS: Our study presented that primary tumor location is an important risk factor for nonmetastatic esophageal NEC patients. Age and pathological type are important risk factors for patients with metastatic esophageal NEC. Nonmetastatic esophageal NEC will benefit from primary tumor resection. Systematic treatment is recommended for metastatic esophageal NEC.

[Retracted] MicroRNA­874 is downregulated in cervical cancer and inhibits cancer progression by directly targeting ETS1.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the Transwell migration assay data shown in Fig. 3A were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article were already under consideration for publication prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 40: 2389­2398, 2018; DOI: 10.3892/or.2018.6624].

Association of thyroid function abnormality and prognosis in non-small-cell lung cancer patients treated with PD-1 inhibitors.

Background: Thyroid function abnormality (TFA) is one of the most common toxicities in non-small-cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors. However, the risk factors related to TFA and the relationship between TFA and prognosis in NSCLC are not fully clarified. Methods: We conducted a retrospective study of patients with advanced NSCLC who were treated with PD-1 inhibitors in Huzhou Central Hospital. Thyroid function test was carried out using electrochemiluminescent bridging immunoassay. The association between TFA and clinical outcome was investigated. Results: A total of 273 patients were included in this study. Patients who experienced TFA had longer progression-free survival (21.9 vs 6.4 months; p < 0.001) and overall survival (44.6 vs 24.1 months; p = 0.02) than patients without TFA. After multivariate analysis, TFA was an independent prognostic factor for progression-free and overall survival (p < 0.05). Conclusion: TFA is associated with better outcome in NSCLC patients who receive immunotherapy.

Many patients with non-small-cell lung cancer are treated with immunotherapy, a type of treatment that uses the body's natural immune system to fight diseases. We conducted a retrospective study of advanced non-small-cell lung cancer patients who were treated with PD-1 inhibitors (a type of immunotherapy) in Huzhou Central Hospital. Thyroid function abnormality (TFA) is one of the common toxicities in patients receiving PD-1 inhibitors. Our study showed that patients who experienced TFA have longer survival times compared with patients without TFA (overall survival, 44.6 vs 24.1 months; p = 0.02). TFA could be an effective predictor of outcome in non-small-cell lung cancer cases being treated with immunotherapy.

Collision carcinoma of endometrial adenocarcinoma and primary serous fallopian tube carcinoma: a case report.

Collision carcinoma is a rare malignancy that generally occurs in cervical, esophageal, pulmonary, and squamous cell cancers. Few studies have been reported involving endometrial adenocarcinoma and fallopian tube carcinoma. We reported the case of a 58-year-old woman who presented because of irregular vaginal bleeding for more than 1 month. Cervical biopsy suggested moderately differentiated cervical adenocarcinoma, and the patient underwent radical hysterectomy under general anesthesia. However, postoperative pathology and immunohistochemical results indicated a collision tumor comprising endometrial adenocarcinoma (grade I) and primary serous fallopian tube carcinoma. According to the treatment principle of multiple primary tumors, a regimen of paclitaxel combined with carboplatin was administered. The patient also underwent local pelvic radiotherapy to treat lymph node metastasis. One month later, the patient developed brain metastases and died.

Nutrition and metabolism status alteration in advanced hepatocellular carcinoma patients treated with anti-PD-1 immunotherapy.

PURPOSE: The aim of this study was to evaluate the nutrition and metabolism status alteration during immunotherapy in advanced hepatocellular carcinoma (HCC) patients. METHODS: Patients with advanced HCC who participated in the clinical trials of single-agent anti-PD-1 immunotherapy or sorafenib were retrospectively included. We analyzed self-comparison of the nutritional and metabolic indices of patients in the anti-PD-1 and sorafenib treatment group. We conducted mutual-comparison of the mentioned indices between the disease progression group and disease control group among anti-PD-1 treatment patients. We further analyzed those indices with statistical differences by partial correlation and survival analysis. RESULTS: Both self-comparison before and after treatment in the anti-PD-1 group and mutual-comparison of disease progression and the control group showed significant differences in multiple indices, but we did not observe significant differences in the sorafenib group. Strikingly, albumin (ALB)/prognostic nutritional index (PNI, calculated by serum albumin and lymphocyte count) decreased distinctly in the immunotherapy disease progression group patients. However, changes in ALB/PNI were not significant in disease progression patients from the sorafenib group or in the disease control patients with immunotherapy. Partial correlation analysis suggested that ALB and PNI were positively correlated with the efficacy of immunotherapy. Furthermore, survival analysis showed that the median progression-free survival and median overall survival of patients in the ALB/PNI decreased group were significantly shorter than those of patients from the ALB/PNI increased group. CONCLUSION: Anti-PD-1 immunotherapy might alter the nutritional and metabolic status in advanced HCC patients. We also should pay attention to the nutritional and metabolic status of patients when drug resistance is detected.

PIM3 Functions as Oncogenic Factor and Promotes the Tumor Growth and Metastasis in Colorectal Cancer.

Colorectal cancer (CRC) is one of the common human malignancies. Discovery and identification of novel therapeutic target is imperative to improve the prognosis of CRC patients. As a member of the PIM family, PIM3 has been found to be overexpressed in a variety of cancerous tumors. In this study, we evaluated the expression of PIM3 in CRC tissues and analyzed the role of PIM3 in CRC. Our results showed that PIM3 expression was significantly higher in CRC tissues compared with adjacent noncancerous tissues. The PIM3 expression level was found to be correlated with advanced disease stage and lymph node metastasis. Moreover, PIM3 was found to be able to predict poor prognosis in CRC patients as an independent factor. In vitro studies also showed that knockdown of PIM3 exhibited inhibitory effect on cell growth, promoted cell apoptosis and dampened invasive capability of HCT116 and SW620 cells. Moreover, PIM3 knockdown was able to delay tumor growth and suppress lung metastasis in xenograft model. Our results indicated that PIM3 is a potential therapeutic target for CRC. Anat Rec, 302:1552-1560, 2019. © 2018 American Association for Anatomy.

MicroRNA­874 is downregulated in cervical cancer and inhibits cancer progression by directly targeting ETS1.

An increasing number of studies have reported that microRNAs (miRNAs) are dysregulated in cervical cancer and serve critical roles in cervical oncogenesis and progression. Therefore, identifying the aberrantly expressed miRNAs implicated in the formation and progression of cervical cancer may provide key clues for the development of effective therapeutic targets in treating patients with this type of malignancy. In the present study, miRNA­874 (miR­874) was downregulated in cervical cancer tissues and cell lines, and this downregulation was associated with International Federation of Gynaecology and Obstetrics stage and lymph node metastasis. The restored expression of miR­874 prohibited the proliferation, migration and invasion, but promoted the apoptosis of cervical cancer cells. In addition, E26 transformation specific­1 (ETS1) was identified as the direct target of miR­874 in cervical cancer. Inhibition of ETS1 served tumour­suppressive roles similar to miR­874 overexpression in cervical cancer cells. A series of rescue experiments revealed that restoring ETS1 expression abolished the tumour­suppressing effects of miR­874 in cervical cancer cells. Taken together, the results of the present study indicated that miR­874 may serve as a tumour suppressor in cervical cancer by directly targeting ETS1. This function suggested that miR­874 holds potential therapeutic applications in treating patients with this type of malignancy.

Simulation of Stress Field during the Selective Laser Melting Process of the Nickel-Based Superalloy, GH4169.

In this paper, GH4169 alloy's distributions of temperature and stress during the selective laser melting (SLM) process were studied. The SLM process is a dynamic process of rapid melting and solidification, and we found there were larger temperature gradients near the turning of scan direction and at the overlap of the scanning line, which produced thermal strain and stress concentration and gave rise to warping deformations. The stresses increased as the distance became further away from the melt pool. There was tensile stress in the most-forming zones, but compressive stress occurred near the melt pool area. When the parts were cooled to room temperature after the SLM process, tensile stress was concentrated around the parts' boundaries. Residual stress along the z direction caused the warping deformations, and although there was tensile stress in the parts' surfaces, but there was compressive stress near the substrate.

Potential screening and early diagnosis method for cancer: Tongue diagnosis.

Tongue diagnosis, as a unique method of traditional Chinese medicine (TCM), was used to discriminate physiological functions and pathological conditions by observing the changes of the tongue and tongue coating. The aims of the present study were to explore a potential screening and early diagnosis method of cancer through evaluating the differences of the images of tongue and tongue coating and the microbiome on the tongue coating. The DS01-B tongue diagnostic information acquisition system was used to photograph and analyze the tongue and tongue coating. The next-generation sequencing technology was used to determine the V2-V4 hypervariable regions of 16S rDNA to investigate the microbiome on the tongue coating. Bioinformatics and statistical methods were used to analyze the microbial community structure and diversity. Comparing with the healthy people, the number of mirror-like tongue, thick tongue coating and the moisture of tongue were increased in cancers. The dominant color of the tongue in the healthy people was reddish while it was purple in the cancers. The relative abundance of Neisseria, Haemophilus, Fusobacterium and Porphyromonas in the healthy people were higher than that in the cancers. We also found 6 kinds of special microorganisms at species level in cancers. The study suggested that tongue diagnosis may provide potential screening and early diagnosis method for cancer.