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As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.
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Objective:To explore the clinicopathological features and prognosis of renal mucinous tubular spindle cell carcinoma (MTSCC).Methods:The clinical data of 16 patients with MTSCC admitted to the First Affiliated Hospital of Zhengzhou University from July 2013 to July 2022 were retrospectively analyzed. There were six male cases and ten female cases. The mean age was (56.4±11.4) years old. Among them, 10 cases were asymptomatic, two complained of hematuria, three complained of lumbar pain, and one complained of lower limb pain. Twelve cases underwent preoperative enhanced CT examination, 6 cases of ultrasound examination, 3 cases of MRI examination, and 1 case of bone scan. Imaging manifestations showed that the masses were round or round-like with clear borders. Two cases combined with hemorrhage and three cases combined with calcification. Five cases showed exophytic growth, 10 cases partially exophytic, and 1 case completely endophytic. The maximum diameter of the tumor was (65.7±27.4) mm. The tumors were located in the left kidney in 11 cases and in the right kidney in 5 cases. The tumors were mildly delayed-enhancing under enhanced CT, long/short T1 signal mixed with long/short T2 signal under MRI, and diffusion-limited high signal under DWI. The tumors were hypoechoic masses without obvious blood flow signals under ultrasound. Twelve cases were diagnosed as renal occupying neoplasms, 2 cases were suggested as lack of blood supply renal tumor, and one was considered renal tumor rupture and bleeding. In one case, a bone scan suggested metastasis to the thoracic spine and pelvis. The metastatic renal tumor was diagnosed, and a renal puncture was performed to clarify the pathology. Eleven patients underwent laparoscopic radical nephrectomy, and 4 patients underwent partial nephrectomy. One case was metastasized without surgery and treated with apatinib mesylate and zoledronic acid.Results:The postoperative pathological specimens showed grayish, grayish-yellow, or grayish-red masses with a soft or medium texture. No perinephric, ureteral, or adrenal invasion was seen in all tumors. Microscopically, the tumor cells were round and ovoid. The tumor cells were arranged in tubular and striated shapes, and mucus pools were locally visible. No sarcomatous component was seen in all tumors. There were 9 patients with pT 1N 0M 0, 6 patients with pT 2N 0M 0, and 1 patient with pT 1N 0M 1. After operation, 2 patients with pT 2N 0M 0, who underwent laparoscopic radical nephrectomy were treated with pazopanib and sunitinib, respectively. All patients were followed up for a median of 50.7(25.8, 75.0)months, 15 patients were free of recurrent metastases, and 1 patient with pre-puncture metastasis died due to tumor progression of multiple pulmonary and bone metastases, with a survival of 16.9 months. Conclusions:Renal MTSCC is rare, mostly found on physical examination, with female patients predominantly, and imaging shows a lack of blood supply tumor. Surgery is the primary treatment method. Partial nephrectomy or radical nephrectomy could be chosen according to the tumor stage, kidney function, and patient's underlying condition, and patients have a good prognosis.
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Objective:To investigate the clinical characteristics and prognostic factors of primary urethral cancer.Methods:The clinical data of 35 patients with primary urethral cancer admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to April 2022 were retrospectively analyzed. There were 12 males (34.3%) and 23 females (65.7%). The average age was 61.1 ± 13.0 years old. The clinical symptoms included 13 cases of urethral obstruction (37.1%), 7 cases of hematuria (20.0%), 6 cases of urethral bleeding (17.1%), 5 cases of urinary tract irritation (14.3%), 1 case of Urinary incontinence (2.9%), 1 case of low back pain (2.9%), 1 case of scrotal ulcer (2.9%), and 1 case (2.9%) by self examination. All patients underwent cystourethroscopy and tissue biopsy. The biopsy pathology showed 16 cases of urothelial carcinoma, 7 cases of squamous carcinoma, 4 cases of adenocarcinoma, 3 cases of malignant melanoma, 1 case of urothelial carcinoma with squamous carcinoma, 1 case of Signet ring cell carcinoma, 1 case of sarcomatoid carcinoma, 1 case of embryonic Rhabdomyosarcoma, and 1 case of epithelioid angiosarcoma. The tumors were located in the proximal urethra in 13 cases (37.1%) and in the distal urethra in 22 cases (62.9%). There were 14 cases (40.0%) with a maximum diameter of less than 3 cm, 16 cases (45.7%) with a diameter of ≥ 3 cm, and 5 cases (14.3%) with mucosal abnormalities. There were 12 cases of T 1 stage, 9 cases of T 2 stage, 7 cases of T 3 stage, and 7 cases of T 4 stage in tumor staging. Imaging evaluation of lymph nodes showed 25 cases of N 0 stage, 2 cases of N 1 stage, and 8 cases of N 2 stage; A total of 11 cases of lymph node biopsy were performed (including 8 cases of intraoperative lymph node dissection and 3 cases of preoperative lymph node biopsy), of which 6 cases had lymph node metastasis, and 1 case was initially diagnosed with distant metastasis. Thirty-one cases underwent surgical treatment, of which 16 cases underwent radical urethrectomy, and 8 cases underwent intraoperative pelvic and bilateral inguinal lymph node dissection, 8 cases underwent resection of urethral tumors, and 7 cases underwent transurethral resection of tumors. Four cases did not undergo surgical treatment, while 1 case had epithelioid angiosarcoma and received radiotherapy combined with chemotherapy, 2 cases received chemotherapy with GC (Gemcitabine+ cisplatin) regimen, and 1 case received immunotherapy with immune checkpoint inhibitors. The risk factors that affected patient prognosis were analyzed. Results:All 35 cases in this group were followed up, with a median follow-up time of 22 (2, 122) months. Seventeen cases survived, 18 cases died, and the overall median survival duration was 23 (13 to not reached) months. The overall 5-year survival rate was 45%. The results of univariate analysis showed that clinical T-stage ( P=0.019), maximum tumor diameter ( P=0.016), and tumor location ( P=0.006) were independent risk factors affecting patient prognosis. Result of multivariate analysis showed that the maximum diameter of the tumor ≥ 3 cm ( HR=2.673, P=0.029) and the proximal location of the tumor ( HR=3.064, P=0.023) were independent risk factors affecting patient survival. Gender, age, treatment method, lymph node dissection, adjuvant radiotherapy, adjuvant chemotherapy, clinical manifestations, pathological type, clinical N staging, and pathological N staging had no significant impact on patient survival rate ( P>0.05). Single factor analysis was conducted on female patients separately, and only tumor location was found to be a prognostic factor ( χ2=17.246, P<0.01). Conclusions:Primary urethral cancer is a rare disease with various symptoms and poor prognosis. The maximum diameter of the tumor ≥3 cm and the tumor located at the proximal end of the urethra are clinical risk factors affecting the prognosis of patients with primary urethral cancer.
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Objective To discuss the clinical diagnosis,treatment and prognosis of malignant melanoma of urinary system.Methods The clinical data of 5 patients with primary malignant melanoma of urinary system were retrospectively analyzed.There were 2 cases of primary melanona of the urethra,3 cases of primary malignant melanoma of the bladder.The diameter of the tumor ranged from 0.9 to 5.1 cm with an average of 3.1 cm.Results Two cases of urethral patients underwent radical resection of urethra.Among 3 cases of bladder,1 cases were in poor condition,and underwent laparoscopic partial cystectomy.In 1 young men,radical resection was refused and only transurethral resection of the bladder tumor was performed.Radical resection of bladder was done in 1 cases.Postoperative pathology showed that the tumor cells of 4 cases were fusiform under microscope,1 case was polygonal.5 cases showed melanin in the cytoplasm and diffuse proliferation of tumor cells,with obvious heterogeneity,cell proliferation index Ki-67 10％-30％.During the follow-up period of 7-30 months (median 19 months),3 patients died of metastasis.Conclusions Malignant melanona of urinary system is rare,with high malignancy and poor prognosis.Targeted therapy and immune therapy has become a new treatment option,which could improve the prognosis of patients.
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Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrino-gen (FIB), platelet aggregation rate and blood clots-fibrinolytic dynamic figure were taken as indexes in the evalua-tion of anticoagulant activity in vivo of active component F2-2 from Eupolyphaga seu Steleophaga. After 5 days of hypodermic injection of adrenaline, the rat model of acute blood stasis was established. Indexes were determined af-ter the model rats were treated with an intragastric administration of F2-2 for 9 days. The results showed that com-pared with the model group, PT/APTT was prolonged, FIB content was decreased, platelet aggregation rate and the largest of blood coagulation were declined after 9 days of intragastric administration in the model group. However, there was no difference on TT. It was concluded that the anticoagulant component F2-2 separated from E. seu Steleophaga showed favorable anticoagulant activity in vivo. However, its mechanism remained unknown and request-ed further researches.
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OBJECTIVE:To compare the clinical effect of different materials for cranioplasty. METHODS:The incidence rate of complication and the degree of moulding satisfaction of patients with skull defect which were repaired using net-added silica gel,auto-cranial bone,three-dimensional Ti frame and digital three-dimensional reconstructed Ti frame were retrospectively analyzed in the Department of Neurosurgery of Xixiang People's Hospital from January 2000 to December 2007. RESULTS:The incidence rate of complication and the degree of moulding satisfaction were 50% and 27.8% in the net-added silica gel group,12.1% and 90.9% in the auto-cranial bone group,27.3% and 45.5% in the three-dimensional Ti frame group,5.6% and 100% in the digital three-dimensional reconstructed Ti frame group,respectively. The incidence rate of complication in the digital three-dimensional reconstructed Ti frame and auto-cranial bone groups was significantly lower than other two groups,while the degree of moulding satisfaction was also significantly different from other two groups (P