Background: The aim was to evaluate the changes of 16S rDNA sequencing and LC-MS metabolomics in breast cancer and explore the growth inhibition of breast cancer cells by Faecalibacterium prausnitzii. Results: Total 49 significantly different flora and 26 different metabolites were screened between two groups, and the correlation was calculated. Relative abudance of Firmicutes and Bacteroidetes were decreased, while relative abundance of verrucomicrobla, proteobacteria and actinobacteria was increased in breast cancer group. Differentially expressed metabolites were mainly enriched in pathways such as linoleic acid metabolism, retrograde endocannabinoid signaling, biosynthesis of unsaturated fatty acids, choline metabolism in cancer and arachidonic acid metabolism. Lipid upregulation was found in breast cancer patients, especially phosphorocholine. The abundance of Faecalibacterium was reduced in breast cancer patients, which was negatively correlated with various phosphorylcholines. Moreover, Faecalibacterium prausnitzii, the most well-known species in Faecalibacterium genus, could inhibit the secretion of interleukin-6 (IL-6) and the phosphorylation of Janus kinases 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) in breast cancer cells. Faecalibacterium prausnitzii also suppressed the proliferation and invasion and promoted the apoptosis of breast cancer cells, while these effects disappeared after adding recombinant human IL-6. Conclusions: Flora-metabolites combined with the flora-bacteria (such as Faecalibacterium combined with phosphorocholine) might a new detection method for breast cancer. Faecalibacterium may be helpful for prevention of breast cancer. Faecalibacterium prausnitzii suppresses the growth of breast cancer cells through inhibition of IL-6/STAT3 pathway.

Major histocompatibility complex (MHC) class I molecules have a crucial role in tumor immune evasion; however, the association of MHC class I molecules with outcomes in cancer patients remains controversial. Nucleotide-binding oligomerization-like receptor family caspase recruitment domain-containing 5 (NLRC5) has been reported to be a MHC class I transactivator. However, the expression and function of NLRC5 in cancer remains to be elucidated. The present study aimed to retrospectively examine NLRC5 expression in human tumor tissues and its association with clinical outcomes of non-small-cell lung cancer (NSCLC) stage III patients. The expression of MHC class I and NLRC5 in NSCLC were detected using immunohistochemistry (IHC). The association between their expression levels was assessed using the Pearson's χ2 test and their association with survival was assessed using Kaplan-Meier analysis and the log-rank test. In addition, the expression of NLRC5 and MHC class I were examined in 323 cases of seven other types of tumors and their correlations were studied. The results revealed that the expression of NLRC5 was correlated with that of MHC class I in NSCLC patients (P=0.008). MHC class I-positive and nuclear NLRC5-positive NSCLC patients were found to have shorter overall survival (OS) rates (log-rank, P=0.032 and P=0.039, respectively). In addition, in the seven different tumor types, there was a significant correlation between MHC class I and NLRC5 nuclear expression (P<0.001) as well as MHC class I and NLRC5 cytoplasmic expression (P=0.003). In conclusion, NLRC5 was demonstrated to be widely expressed in eight tumor tissues and its expression was correlated with that of MHC class I. Of note, nuclear NLRC5-negative and MHC class I-negative stage III NSCLC patients had improved OS rates compared to those with positive expression. Therefore, NLRC5 and MHC class I may be negative prognostic indicators in NSCLC stage III patients.

Background: Bladder cancer with high expression of human epidermal growth factor receptor-2 (HER2) is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2-positive MIBC, the efficacy of cisplatin-based NAC is unsatisfactory, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity need to be explored in the neoadjuvant setting for this population.Methods: HOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study aiming to evaluate the safety and efficacy of RC48-ADC (disitamab vedotin (DV)), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2-positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathology- and imaging-diagnosed HER2 positive (immunohistochemistry status 3+ or 2+ or 1+) MIBC were recruited. Of these patients, six were enrolled in the dose-escalation phase (three patients in the RC48-ADC 1.5 mg/kg group and three patients in the 2.0 mg/kg group), and 45 patients were enrolled in the phase II study (the expected recommended phase II dose for RC48-ADC was 2.0 mg/kg). Patients without disease progression received radical cystectomy or bladder-sparing therapies as their preference after neoadjuvant treatment. The primary endpoints were clinical complete remission rate (cCR rate; T0/Ta/Tis), pathological complete remission rate (pCR rate), and safety. The secondary endpoints were overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and quality of life.Discussion: The HOPE-03 trial provides a description of the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2-positive locally advanced urothelial MIBC, and the efficacy is explored as well in this population.Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=137111, identifier ChiCTR2200060153.

Background and Aims: Primary adenosquamous carcinoma (ASC) is a rare liver malignancy with very little data published so far. We describe the clinical characteristics of this tumor and analyze its survival pattern to improve the diagnosis and treatment.Materials and Methods: This study collected data of 15 patients with primary hepatic ASC in our hospital within 10 years (from 2009 to 2018). We analyzed the clinical characteristics, imaging data, treatment, and survival of ASC in the study. Two of these cases have been reported.Results: The common clinical symptoms of hepatic ASC are liver pain and jaundice. Laboratory examination showed that carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) increased, but Alpha-FetoProtein (AFP) did not. Primary hepatic ASC is a rare subtype of intrahepatic cholangiocarcinoma (ICC) and meets the requirements of pathological diagnosis: CK20 (-), CK7 (+), CK19 (+), and p63 (+). Of the 15 patients, 11 were treated surgically, of which 3 patients received adjuvant chemotherapy. The prognosis of ASC patients is poor with a median survival time (MST) of 6 months (range: 2 to 15). The duration of MST in surgically treated patients was longer than that of nonsurgical patients (7.0 months vs. 3.0 months). Patients that received adjuvant chemotherapy survived longer (MST: 15 months). Patients with lymph node metastasis had a worse prognosis.Conclusion: Primary hepatic ASC is a rare malignant tumor with a poor prognosis. Radical surgery may be an effective treatment for prolonging survival. Surgical treatment combined with adjuvant therapy may further improve survival.

Radical prostatectomy (prostate removal) is a standard treatment for clinically localized prostate cancer and is often followed by postoperative radiotherapy. Postoperative radiotherapy requires accurate delineation of the clinical target volume (CTV) and lymph node drainage area (LNA) on computed tomography (CT) images. However, the CTV contour cannot be determined by the simple prostate expansion after resection of the prostate in the CT image. Constrained by this factor, the manual delineation process in postoperative radiotherapy is more time-consuming and challenging than in radical radiotherapy. In addition, CTV and LNA have no boundaries that can be distinguished by pixel values in CT images, and existing automatic segmentation models cannot get satisfactory results. Radiation oncologists generally determine CTV and LNA profiles according to clinical consensus and guidelines regarding surrounding organs at risk (OARs). In this work, we design a cascade segmentation block to explicitly establish correlations between CTV, LNA, and OARs, leveraging OARs features to guide CTV and LNA segmentation. Furthermore, inspired by the success of the self-attention mechanism and self-supervised learning, we adopt SwinTransformer as our backbone and propose a pure SwinTransformer-based segmentation network with self-supervised learning strategies. We performed extensive quantitative and qualitative evaluations of the proposed method. Compared to other competitive segmentation models, our model shows higher dice scores with minor standard deviations, and the detailed visualization results are more consistent with the ground truth. We believe this work can provide a feasible solution to this problem, making the postoperative radiotherapy process more efficient.