Patients preoperatively diagnosed with ductal carcinoma in situ (DCIS) by core needle biopsy (CNB) exhibit a significant risk for upstaging on final pathology, which leads to major concerns of whether axillary staging is required at the primary operation. The present study aimed to identify clinicopathological factors associated with upstaging in patients preoperatively diagnosed with DCIS by CNB.The present study enrolled 604 patients (cN0M0) with a preoperative diagnosis of pure DCIS by CNB, who underwent axillary staging between August 2006 and December 2015, at Fudan University Shanghai Cancer Center (Shanghai, China). Predictive factors of upstaging were analyzed retrospectively.Of the 604 patients, 20.03% (n = 121) and 31.95% (n = 193) were upstaged to DCIS with microinvasion (DCISM) and invasive breast cancer (IBC) on final pathology, respectively. Larger tumor size on ultrasonography (> 2 cm) was independently associated with upstaging [odds ratio (OR) 1.558,P = 0.014]. Additionally, patients in lower breast imaging reporting and data system (BI-RADS) categories were less likely to be upstaged (4B vs. 5: OR 0.435, P = 0.002; 4C vs. 5: OR 0.502, P = 0.001). Overall, axillary metastasis occurred in 6.79% (n = 41) of patients. Among patients with axillary metastasis, 1.38% (4/290), 3.31% (4/121) and 17.10% (33/193) were in the DCIS, DCISM, and IBC groups, respectively.For patients initially diagnosed with DCIS by CNB, larger tumor size on ultrasonography (> 2 cm) and higher BI-RADS category were independent predictive factors of upstaging on final pathology. Thus, axillary staging in patients with smaller tumor sizes and lower BI-RADS category may be omitted, with little downstream risk for upstaging.
The huge market potential of some fast growing markets attract many international organizations’ attention, especially China, as a huge automobile market is one of the most typical examples. Theref ...
Cellular immunotherapy has become a potential therapeutic method for different diseases.Herein, we reported clinical trial results of Cytokine-induced killer (CIK) cells used for patients with hepatitis B, cirrhosis and liver cancers from 2000 to 2015.Results showed CIK cell therapeutic effects were closely positively associated with CIK cell numbers, treated times and HBV genotypes.Different stages of HBV patients treated with > 10 10 CIK cells per time for more than ten times exhibited remarkable decrease of HBV DNA numbers (P < 0.01), ALT and AST gradually recovered to normal scope, cytokine factors such as IFN-g, IL-1b, IL-2, IL-4, IL-6, IL-10, IL-22 and IL-27 exhibited obvious increase, lifespan of patients with cirrhosis and hepatocellular carcinoma were extended, and that all the patients felt better in sleep, diet and pain during the period of CIK therapy.In conclusion, CIK cell therapy is a good alternative therapeutic method and can be effectively used for treatment of different stages of HBV patients.
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial–mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK–STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target.
To introduce the treatment of severe obstructive sleep apnea-hypopnea syndrome (OSAHS) with Repose bone screw system and to evaluate the treating effect.Thirty-two patients with severe OSAHS (Friedman classification II, III) were treated with tongue ablation + uvulopalatopharyngoplasty + hard palate shortening + Repose suspension. All patients were followed-up for 6 months. Apnea hypopnea index (AHI), lowest oxygen percent saturation (LSaO₂), body mass index (BMI), vallecula epiglottic-lateral pharyngeal wall (V-LPW) and pharyngeal airway space (PAS) were used for the diagnosis and evaluation.The AHI in 32 patients reduced from (78.3 +/- 11.6)/h to (18.4 +/- 12.5)/h (x(-) +/- s), t = 13.5, P = 0.000. The LSaO₂ increased from (0.632 +/- 0.007) to (0.794 +/- 0.006), t = 4.1, P = 0.000. The BMI was statistical indiscriminate. The V-LPW increased from (12.1 +/- 3.2) mm to (16.9 +/- 2.6) mm (t = 2.5, P = 0.014). PAS increased from (9.2 +/- 3.3) mm to (15.6 +/- 2.4) mm (t = 7.6, P = 0.000). The total effective rate was 93.8%. Three genioglossus stabilization patients complained about foreign body sensation in the mouth floor 3 - 7 days after procedures, which disappeared in 6 months. One genioglossus stabilization patients complained about mandibular osteomyelitis 3 months after procedures, which recovered after anti-inflammatory treatment for 5 days. One genioglossus stabilization patients appeared hypoglossia bleeding, which stopped after compression. One hyoid suspension patients showed haematoma of submandibular region and cured after incision and drainage.Repose system was an effective method, safe, simple, with few complications.
Nasopharyngeal carcinoma (NPC) is known for its high-metastatic potential. Here we report the identification of the proteoglycan serglycin as a functionally significant regulator of metastasis in this setting. Comparative genomic expression profiling of NPC cell line clones with high- and low-metastatic potential revealed the serglycin gene (SRGN) as one of the most upregulated genes in highly metastatic cells. RNAi-mediated inhibition of serglycin expression blocked serglycin secretion and the invasive motility of highly metastatic cells, reducing metastatic capacity in vivo. Conversely, serglycin overexpression in poorly metastatic cells increased their motile behavior and metastatic capacity in vivo. Growth rate was not influenced by serglycin in either highly or poorly metastatic cells. Secreted but not bacterial recombinant serglycin promoted motile behavior, suggesting a critical role for glycosylation in serglycin activity. Serglycin inhibition was associated with reduced expression of vimentin but not other epithelial-mesenchymal transition proteins. In clinical specimens, serglycin expression was elevated significantly in liver metastases from NPC relative to primary NPC tumors. We evaluated the prognostic value of serglycin by immunohistochemical staining of tissue microarrays from 263 NPC patients followed by multivariate analyses. High serglycin expression in primary NPC was found to be an unfavorable independent indicator of distant metastasis-free and disease-free survival. Our findings establish that glycosylated serglycin regulates NPC metastasis via autocrine and paracrine routes, and that it serves as an independent prognostic indicator of metastasis-free survival and disease-free survival in NPC patients.
Purpose Recurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level. Experimental design We performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments. Results reRCC had reduced CD8 + T cells but increased cancer-associated fibroblasts (CAFs) infiltration compared with pRCC. Reduced CD8 + T cells and increased CAFs infiltration were significantly associated with a worse response from immunotherapy. Remarkably, CAFs showed substantial expression of LGALS1 (Gal1). In vitro, CAFs could induce CD8 + T cells apoptosis via Gal1. In vivo, knockdown of Gal1 in CAFs suppressed tumor growth, increased CD8 + T cells infiltration, reduced the proportion of apoptotic CD8 + T cells and enhanced the efficacy of immunotherapy. Conclusions We delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8 + T cells via Gal1. Targeting Gal1 combined with anti-PD1 showed promising efficacy in treating RCC.
This paper presents a novel low-energymemory design technique based on variable analysis for on-chip data memory (RAM) in application-specific systems, which called VAbM technique. It targets the exploitation of both data locality and effective data width of variables to reduce energy consumed by data transfer and storage. Variables with higher access frequency and smaller effective data width are assigned into a smaller low-energy memory with fewer bit lines and word lines, placed closer the processor. Under constraints of the number of memory banks, VAbM technique use variable analysis results to perform allocating and assigning on-chip RAM into multiple banks, which have different size with different number of word lines and different number of bit lines tailored to each application requirements. Experimental results with several real embedded applications demonstrate significant energy reduction up to 64.8% over monolithic memory, and 27.7% compared to memory designed by memory banking technique. key words: Low Energy, Memory Organization, Variable Analysis, Application-Specific System
Objective
To investigate the risk factors predicting pathology grade upgrading after radical prostatectomy using the 2014 International Society of Urologic Pathology (ISUP) grading system.
Methods
A total of 205 patients who underwent biopsy and radical prostatectomy from January 2017 to December 2018 were reviewed retrospectively. The median and range of the patients’age, PSA level, prostate volume, number of biopsy core examined, Gleason score and ISUP grade were 66(45-81)years old, 17.16(0.89-1254.00)ng/ml, 36.4(4.1-152.1)ml, 10(1-15), 7(6-10), and 3(1-5) respectively. The patients were divided into group of upgrading ISUP grade and group without upgrading ISUP grade. Multivariate Logistic regression analysis and receiving operating characteristic curve analysis were performed to identify predictors of ISUP upgrading and determine the optimal cut off value respectively.
Result
The median and range of Gleason score and ISUP grade after radical prostatectomy were 7(6-10), and 3(1-5) respectively. The radical prostatectomy ISUP grade upgraded in 73(35.6%)out of 205 cases when compared with biopsy ISUP grade. Radical prostatectomy ISUP grades were concordant in 91 cases (44.4%) and downgraded in 41 cases(20.0%). Of 101 with biopsy ISUP grades less than or equal to 2, the ISUP grade of radical prostatectomy upgraded in 58 cases(57.4%), while radical prostatectomy ISUP grade upgraded in only 18(26.9%) of 67 patients with biopsy ISUP grades of 3 or 4. Biopsy ISUP grades represent an independent predictor for ISUP grade upgrading after radical prostatectomy(OR=0.496, P<0.001).
Conclusion
Patients with biopsy ISUP grades less than or equal to 2 are at great risk of ISUP grade upgrading after radical prostatectomy.
Key words:
Prostatic neoplasms; Prostate cancer; Radical prostatectomy; Biopsy; Pathology upgrading
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