Endometrial cancer (EC) derived G3BP1 overexpression and mutant promote EC tumorigenesis and metastasis via SPOP/ERα axis.

BACKGROUND: Ras-GTPase-activating protein binding protein 1 (G3BP1) is an oncogenic factor, which highly expressed in a variety of cancers. In recent years, G3BP1 has been reported to promote the development of prostate cancer by inhibiting the degradation of AR through inhibiting SPOP. However, whether G3BP1 contributes in a similar manner to the abnormal accumulation of ERα, which is also an important target for hormone therapy, remains unknown. This article addresses this issue and explores potential mechanisms. METHODS: Bioinformatics tools were used for G3BP1 expression analysis, survival analysis, and clinical association analysis. Immunohistochemical staining was used to examine the correlation between G3BP1 and ERα in EC patients. In addition, western blot and co-immunoprecipitation were used to detect the half-life of G3BP1 and mutant, and the effect of G3BP1 and mutant on the ubiquitination and degradation of ERα mediated by SPOP. Then, the oncogenic functions of G3BP1 dependent on the SPOP/ERα axis were determined by CCK8 cell proliferation assay, colony formation assay and cell migration assay. Finally, we established the EC cells treated or untreated with fulvestrant, exploring the possibility of fulvestrant combined with the reduction of G3BP1 to improve the efficacy of fulvestrant. RESULTS: G3BP1 is abnormally high expressed and characterized by high-frequency mutation in EC. In addition, there is a positive correlation between G3BP1 protein and ERα protein. Mechanistically, both G3BP1 and mutant, the latter is displaying the longer half-life, competitively bind SPOP with ERα, thereby inhibiting SPOP-mediated ubiquitination and degradation of ERα. Functionally, G3BP1 and mutant promote the proliferation and migration of EC cells by regulating the G3BP1/SPOP/ERα axis. However, fulvestrant can reverse the cancer-promoting effects of G3BP1 and mutant. CONCLUSIONS: G3BP1 and its mutant positively regulate ERα signaling pathway by inhibiting SPOP-mediated ubiquitination and degradation of ERα, indicating the promising effect of fulvestrant on the suppression the occurrence and development of EC with high expressed G3BP1 and G3BP1 mutants. Video Abstract.

Potential value of tumor stiffness and sE-cadherin in predicting the response to neoadjuvant therapy in HER2-positive breast cancers.

Background: This prospective study compared the diagnostic value of tumor stiffness and serum soluble E-cadherin (sE-cadherin) expression for predicting response to neoadjuvant therapy in HER2-positive breast cancers. Methods: 112 patients with early or locally advanced HER2-positive breast cancer were enrolled. Maximum stiffness (Emax), mean stiffness (Emean) and their relative changes were assessed at t0 and t2. sE-cadherin levels were analyzed using ELISA. Pathological complete response was defined as no invasive disease in the breast and axilla (ypT0/is, ypN0) after surgery. The ability of tumor stiffness, sE-cadherin and the combination of ΔEmean (the relative change in Emean after the second cycle of neoadjuvant therapy) and sE-cadherin in predicting tumor responses was assessed using receiver operating characteristic curves and the Z-test. Results: Tumor stiffness and sE-cadherin decreased during neoadjuvant therapy. ΔEmean and sE-cadherin revealed the best predictive performance, with areas under the curve (AUCs) of 0.843 and 0.857, respectively. No significant differences in AUCs were reported between ΔEmean and sE-cadherin (p = 0.795). The combined use of ΔEmean and sE-cadherin showed the highest sensitivity and specificity (93.22 and 90.57%, respectively), with an AUC of 0.937. Conclusion: The combination of ΔEmean and sE-cadherin may improve the predictive power of each single factor. Although further verification is required, this study may promote noninvasive prediction of neoadjuvant therapy responses and help personalize the treatment regimen.

HER2 positivity in breast cancer is associated with a poor prognosis and shortened overall survival. For patients with HER2-positive early breast cancer, the standard neoadjuvant treatment consists of trastuzumab and pertuzumab plus docetaxel, and produces high response rates. In spite of the success of neoadjuvant therapy, some patients show no response due to drug resistance. An accurate prediction of the response of early HER2-positive breast cancer to neoadjuvant therapy would allow the modification of treatment with a response-guided strategy, thereby improving overall survival. Shear wave elastography and serum soluble E-cadherin may provide useful data on responsiveness to neoadjuvant therapy in breast cancers. This study was conducted to compare the diagnostic value of tumor stiffness and soluble E-cadherin expression for predicting the response to neoadjuvant therapy in HER2-positive breast cancers. Although these results will require further verification with larger studies, this study may promote noninvasive prediction of neoadjuvant therapy responses and help personalize the treatment regimen.

Comparison of indocyanine green and carbon nanoparticles in endoscopic techniques for central lymph nodes dissection in patients with papillary thyroid cancer.

BACKGROUND: Injection of carbon nanoparticle (CN) into the thyroid gland is used to stain CLNs in endoscopic surgery of patients with papillary thyroid cancer (PTC). The black-dye technique facilitates the central lymph nodes (CLNs) harvest and parathyroid protection, but improper handling of CN during injection leads to unwanted staining of surrounding tissues and increases the difficulty in anatomical identification. Therefore, a new method is needed to overcome this problem. METHODS: Forty-eight patients with PTC underwent endoscopic thyroidectomy via breast approach. Patients were randomized into the indocyanine green (ICG) group (Group ICG; n = 23) and CN group (Group CN; n = 25). After thyroid gland exposure, ICG was injected into the thyroid lobes. Fluorescent CLNs were identified and dissected in Group ICG. In Group CN, CN was used instead. Black dyed CLNs were harvested. The following was compared between groups: demographic characteristics, surgical time, drainage amount, hospital stay duration, number of CLNs harvested, frequency of postoperative hoarseness and hypothyroidism, and surgical cost. RESULTS: Group ICG showed decreased hypoparathyroidism frequency than Group CN (1/23 vs. 7/25, p = 0.028) and more harvested CLNs (4.6 ± 1.0 vs. 3.8 ± 1.2, p = 0.020). There was no difference between drainage amount, hospital stay duration, and frequency of postoperative hoarseness. The cost of Group ICG was less than that of Group CN (p = 0). CONCLUSION: Injection of ICG into the thyroid gland using fluorescence imaging in endoscopic surgery in patients with PTC is safer and more effective in identifying CLNs than injection with CN. This novel method can lead to improved identification and subsequent harvesting of CLNs.

Molecular mechanisms of Tetrastigma hemsleyanum Diels&Gilg against lung squamous cell carcinoma: From computational biology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum （T. hemsleyanum）, valued in traditional medicine for its potential to boost immunity and combat tumors, contains uncharacterized active compounds and mechanisms. This represents a significant gap in our understanding of its ethnopharmacological relevance. AIM OF THE STUDY: To involve the mechanism of anti-lung cancer effect of T. hemsleyanum by means of experiment and bioinformatics analysis. MATERIALS AND METHODS: The anticancer mechanism of T. hemsleyanum against lung squamous carcinoma (LUSC) in zebrafish was investigated. The LUSC model was established by injecting NCI-H2170 cells in the zebrafish and evaluating its anti-tumor efficacy. Next, component targets and key genes were obtained by molecular complex detection (MCODE) analysis and protein-protein interaction (PPI) network analysis. Component analysis of T. hemsleyanum was performed by UPLC-Q-TOF-MS. Molecular docking was used to simulate the binding activities of key potential active components to core targets were simulated using. Prognostic and pan-cancer analyses were then performed to validate the signaling pathways involved in the prognostic genes using gene set enrichment analysis (GSEA). Subsequently, Molecular dynamics simulations were then performed for key active components and core targets. Finally, cellular experiments were used to verify the expression of glutamate metabotropic receptor 3 (GRM3) and glutamate metabotropic receptor 7 (GRM7) in the anticancer effect exerted of T. hemsleyanum. RESULTS: We experimentally confirmed the inhibitory effect of T. hemsleyanum on LUSC by transplantation of NCI-H2170 cells into zebrafish. There are 20 main compounds in T. hemsleyanum, such as procyanidin B1, catechin, quercetin, and kaempferol, etc. A total of 186 component targets of T. hemsleyanum and sixteen hub genes were screened by PPI network and MCODE analyses. Molecular docking and molecular dynamics simulation results showed that Gingerglycolipid B and Rutin had higher affinity with GRM3 and GRM7, respectively. Prognostic analysis, Pan-cancer analysis and verification experiment also confirmed that GRM3 and GRM7 were targets for T. hemsleyanum to exert anti-tumor effects and to participate in immune and mutation processes. In vitro experiments suggested that the inhibitory effect of T. hemsleyanum on cancer cells was correlated with GRM3 and GRM7. CONCLUSION: In vivo, in vitro and in silico results confirmed the potential anticancer effects against LUSC of T. hemsleyanum, which further consolidated the claim of its traditional uses.

Waldenström macroglobulinemia presenting as bilateral bloody pleural effusion: A case report.

RATIONALE: Pleural effusion, especially bilateral bloody pleural effusion, is a rare complication of Waldenström macroglobulinemia (WM). Pleural effusion in patients with WM has many causes, such as infection, tumor invasion of the pleura, and rupture of the thoracic duct or its branches. Patients with WM presenting to the respiratory department with chest tightness and shortness of breath need more differential diagnosis by respiratory physicians, which is helpful for effective treatment. Herein, we present a case of MV diagnosis in a patient with bilateral bloody pleural effusion. PATIENT CONCERN: Our patient is a 59-year-old man with WM presenting as having bilateral bloody pleural effusion. INTERVENTIONS: The patient was treated with pleural effusion drainage. After confirming the diagnosis, the patient was treated with rituximab, cyclophosphamide, and dexamethasone. OUTCOMES: Following these treatments, the patient's symptoms improved, and ultrasound showed a decrease in pleural effusion. LESSONS: Despite its favorable prognosis, the cause of pleural effusion in a patient with WM can be challenging to diagnose. The cause of pleural effusion should be considered a differential diagnosis when diagnosing patients diagnosed with WM.

Expression of both matrix metalloproteinase-2 and its tissue inhibitor-2 in tunica media of radial artery in uremic patients.

OBJECTIVE: To investigate the expression and clinical significance of both matrix metalloproteinase-2 (MMP-2) and its tissue inhibitor (tissue inhibitor of metalloproteinase-2 (TIMP-2)) in tunica media of radial artery in uremic patients. METHODS: The modified radial arteries from 80 uremic patients during internal arteriovenous fistula surgery were selected and used as experimental specimens. The calcification of tunica media was observed by alizarin red staining, and the expression status of MMP-2, TIMP-2, osteoprotegerin (OPG), and osteopontin (OPN) in tunica media of radial arteries of these patients was detected by immunohistochemical method. The semiquantitative analysis and comparison were conducted based on the calcification grading and the expression of each test protein in tunica media of radial artery. RESULTS: Of the 80 cases of radial artery specimens, 37 cases were presented with various degrees of calcification of tunica media, and the calcification rate was 46.25%; the expression of MMP-2, TIMP-2, OPG, and OPN could be detected in the calcificated tunica media of the radial artery and was positively correlated with the degree of vascular calcification (p < 0.05). CONCLUSION: The incidence of vascular calcification in uremic patients was high. The occurrence of calcification in tunica media of the radial artery was correlated with the expression of MMP-2 and TIMP-2.

Unexpected form of ischemic colitis: A case report.

Ischemic colitis (IC) is an ischemic injury to the colon caused by an occlusive arterial blood supply or blocked venous return. Colonoscopic manifestations most frequently include colonic mucosal edema and erosion, while tubular channels are rare. It is also known as colon cast, and doctors often misdiagnose it when they encounter it. The present study presents a rare form of IC. An 80-year-old man visited The Affiliated People's Hospital of Ningbo University (Ningbo, China) due to abdominal pain and bloody stools. He had no significant comorbidities and had not taken medication. Physical examination suggested tenderness in the left lower abdomen. Abdominal computed tomography (CT) showed thickening of the sigmoid colon wall. Laboratory tests showed positive fecal occult blood, whereas routine blood tests, including blood coagulation, were normal. Diagnostic colonoscopy revealed sigmoid colon narrowing. There was a long strip of tissue in the sigmoid with a cystic and smooth head, the base of the pedicle was edematous and anabrotic. Abdominal CT angiography revealed no abnormality of the mesenteric artery. The day after colonoscopy, the patient expelled a 17-cm strip of tissue from his anus. Pathological examination revealed inflammatory necrotic colonic mucosa. After 1 week, repeat colonoscopy revealed the strip had been shed, the sigmoid mucosa was edematous and anabrotic, but other intestinal segments were normal.

Relationship between indium exposure and oxidative damage in workers in indium tin oxide production plants.

PURPOSE: The study aimed to assess the relationship between indium exposure and surfactant protein and any oxidative damage in indium tin oxide (ITO)-exposed workers. METHODS: The study was conducted in two typical ITO-manufacturing plants in Taiwan. One hundred and seventy manufacturing workers and 132 administrators were recruited. RESULTS: The geometric mean serum indium (S-In) level in the workers of the manufacturing department was 1.26 µg/l, which was significantly higher than those in the administrative department (0.72 µg/l). The S-In levels of 49 workers were higher than 3 µg/l (49/302, 16.2%), exceeding an occupational exposure limit suggested by the Japan Society for Occupational Health. Significant positive relationships were found between S-In and surfactant protein A (SP-A), and surfactant protein D (SP-D) levels. SP-A and SP-D levels were elevated significantly in the workers with moderately high indium exposure. CONCLUSION: The present study indicates a significant elevating trend of SP-A and SP-D levels in ITO-manufacturing workers, which are sensitive markers of interstitial lung disease. Though the indium exposure is not directly linked to all indicators of oxidative DNA damage, the ITO-manufacturing workplace is suggested to be related to oxidative DNA damage for the workers in the current study. Therefore, in addition to the indium exposure, there might be other occupational hazards in the ITO workplace to cause oxidative damage.

Predictors of impaired effectiveness of carbon nanoparticle-based central lymph node tracing in patients who underwent surgery for papillary thyroid cancer: A retrospective cohort study.

Carbon nanoparticles (CNs) are used in papillary thyroid cancer (PTC) surgery to facilitate central lymph node dissection (CLND) and protect the parathyroid glands (PGs). However, some cases develop hypoparathyroidism after using CNs. This cohort study was undertaken to explore the predictors of the reduced effectiveness of CNs. Data on patients with PTC who underwent surgery wherein CNs were used during CLND were reviewed retrospectively. Patients who did not develop hypoparathyroidism and developed hypoparathyroidism were classified into Group A and B, respectively. Demographic and clinical characteristics were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed on related variables. The receiver operating characteristic curve was used to evaluate the predictors of the binary logistic model and the cutoff value of each predictor was obtained. A total of 265 patients were included. Compared with Group A, the patients in Group B had a higher body mass index (BMI) (P = .003), were more frequently associated with Hashimoto thyroiditis (HT) (P = .001), and tumors were larger in size (P = .026). Multivariate logistic regression analyses were performed on these variables and showed that HT (P = .001) and tumor size (P = .001) predicted the impaired role of CNs. CNs are not always useful in protecting PG function in patients who undergo CLND for PTC. In patients with coexisting HT (blood thyroid peroxidase antibody [TPOAb] level higher than 44.0 IU/mL or blood anti-thyroglobulin antibody [ATG] level higher than 125.0 IU/mL) or a tumor size exceeding 1.1 cm in diameter, the protective role of CNs may be impaired.

Case report: Systemic muscle involvement as the primary clinical manifestation of chronic active Epstein-Barr virus infection: A case-based review.

Chronic active Epstein-Barr virus infection (CAEBV) is common in Asian countries and characterized by recurrent or persistent infectious mononucleosis-like symptoms. Here, we describe a rare case of CAEBV-associated generalized myositis with extranodal NK/T-cell lymphoma, who initially presented with swelling and muscle soreness in the extremities and was diagnosed as polymyositis at the initial stage. CAEBV-associated generalized myositis is different from polymyositis and other types of myositis. Furthermore, it is prone to lymphoma with poor prognosis.

Mixed neuroendocrine carcinoma of the gastric stump: A case report.

BACKGROUND: Gastric stump cancer, also known as gastric remnant cancer (GRC), is one of the main complications of postgastrectomy syndrome, which usually occurs following Billroth II reconstruction. The predominant histological subtype of GRC is adenocarcinoma, whereas neuroendocrine carcinoma is relatively rare. In particular, there are few recently reported cases of mixed neuroendocrine carcinoma (MNEC) in the English literature. Here, we present an extremely rare case of MNEC of the gastric stump. CASE SUMMARY: A 59-year-old patient presented to our department owing to chronic constipation. He had undergone subtotal gastric resection 35 years prior to admission because of benign peptic ulcer. After admission, the patient underwent several tests, and gastroendoscopy showed evidence of Billroth II gastrectomy and local thickening of the gastric stump mucosa at the gastrojejunostomy site, with bile reflux; pathological biopsy revealed adenocarcinoma. He was then diagnosed with GRC and underwent total gastrectomy, D2 Lymphadenectomy, and esophagojejunal Roux-en-Y reconstruction. Histopathological examination of the specimen identified MNEC comprising MNEC (60%), adenocarcinoma (30%), and squamous cell carcinoma (10%). Postoperative adjuvant chemotherapy was initiated on September 17, 2020. Taxol plus cisplatin was administered for only one cycle because of severe liver function damage, and the regimen was changed to etoposide plus cisplatin on October 10, 2020 for five cycles. The patient recovered, with no recurrence after 6 mo of follow-up. CONCLUSION: Gastric MNECs (GMNECs) is a rare type of GRC. This study presented the unusual occurrence of GMNEC in the gastric stump. This case will contribute to improvements in our understanding of the carcinogenesis, biology, pathology, and behavior of GMNEC and GRC.

Clinical feasibility of imaging with indocyanine green combined with carbon nanoparticles for sentinel lymph node identification in papillary thyroid microcarcinoma.

BACKGROUND: Although several previous studies demonstrated the feasibility and efficacy of indocyanine green (ICG) for thyroid cancer surgery, ICG was administered through venous injection and focused on parathyroid gland protection. We thus aimed to study the feasibility of imaging using ICG combined with carbon nanoparticles (CNs) in the identification of sentinel lymph nodes (SLNs) in patients diagnosed with papillary thyroid microcarcinoma (PTMC). METHODS: Two approaches were applied to detect lymph nodes in PTMC surgery. Patients were randomized into 2 groups. ICG and CNs were injected into the thyroid in Group A. In Group B, only CNs was injected. Black-stained or fluorescent nodes observed using near-infrared fluorescence imaging systems were defined as SLNs. SLN and central lymph node (CLN) dissection was completed in both groups. The pathological and postoperative outcomes were compared between 2 groups. RESULTS: There were 40 patients in Group A and 60 in Group B. A total of 138 SLNs were identified; 72 and 66 SLNs were detected and dissected in Groups A and B, respectively. The number of SLNs identified (per patient) in Group A was higher than that in Group B (P = .027). The number of harvested CLNs was 161 and 192 in Groups A and B, respectively, out of which 45 and 48 lymph nodes with metastasis were confirmed by permanent pathology. The CLN metastatic rate in Group A was higher than that in Group B (P = .048). CONCLUSION: Imaging using ICG combined CNs is feasible and safe for SLN identification in PTMC patients. Compared with using only CNs, more SLNs can be removed and more metastatic lymph nodes can be confirmed when using the combined method. Although the combined method appears to accurately stage tumors, further research is needed.

The time window of intermittent hypoxia intervention after middle cerebral artery occlusion.

It was known that preconditioning hypoxia can reduce the damage caused by ischemia. However, there was no study investigating the effects of intermittent hypoxia post ischemia. The purpose of this study was to investigate the time window for administering the hypoxia for beneficial effects after cerebral ischemic damage. According to the recovery days post transient middle cerebral occlusion (MCAO), the rats were randomly assigned to one of the 4 groups (n = 20 for each group, I, II, III, and IV). Rats were then assigned to one of the 2 subgroups (a and b). Rats in group Ia, IIa, IIIa, and IVa were exposed to 7 days of intermittent hypoxia (12% O2 for 4 hours per day) after recovery 1, 2, 3, and 7 days from MCAO, respectively. Rats in group Ib, IIb, IIIb, and IVb rested for 7 days in the same hypoxia chamber without hypoxia exposure after 1, 2, 3, and 7 days post MCAO, respectively. The mortality rate of rats received hypoxia after 1 day' and 2 days' recovery post MCAO was 40% (P = 0.087) and 10% (P = 0.5), respectively. The mean infarct volume of rats received hypoxia after 7 days' recovery was significantly less than that of the comparable control group (9.23 +/- 0.71% vs. 13.32 +/- 1.26%; P = 0.013), and no rats died in this group. In summary, intermittent hypoxia intervention for 7 days after 7 days of recovery post ischemia can reduce the infract volume, and does not increase the mortality rate. According to our results, we suggest that 7 days post ischemia may be the suitable time to begin the intermittent hypoxia intervention to enhance the recovery from cerebral ischemia.

miR-200a suppresses cell growth and migration by targeting MACC1 and predicts prognosis in hepatocellular carcinoma.

miR-200a suppresses tumor development and progression; however, its role in tumor growth and metastasis of hepatocellular carcinoma (HCC) and the underlying mechanism have not been elucidated. In the present study, we identified that miR-200a was markedly downregulated in HCC and exerted suppressive effects on tumor cell growth and metastasis. We identified that miR-200a suppressed tumor growth and metastasis by directly targeting MACC1. In addition, HCC patients with low miR-200a expression had significantly worse prognosis than those with high expression of miR-200a. These findings suggest that miR-200a may be recognized as a novel potential biomarker to predict the survival of patients with HCCs following liver transplantation.