Association of mismatch repair deficiency in endometrial cancer with 18F-FDG PET/CT and clinicopathological features and their prognostic value.

PURPOSE: Identification of the mismatch repair (MMR) deficiency in endometrial cancer (EC) may aid in the screening of patients who may benefit from immunotherapy. Our goal was to investigate the relationship between MMR status and 18F-FDG PET/CT metabolic parameters and clinicopathological features in patients with EC, as well as to explore their prognostic value. METHODS: This retrospective study included 106 EC patients who were classified as MMR deficient (dMMR) or MMR proficient (pMMR) group based on MMR protein expression status evaluated by immunohistochemistry. Clinicopathological characteristics and PET metabolic parameters were compared between the dMMR and pMMR groups, and their relationships with MMR status and prognosis were evaluated. RESULTS: Of 106 EC patients, 30 patients (28.1%) had dMMR, while 76 (71.7%) had pMMR. Compared with the pMMR group, the dMMR group showed a lower prevalence of overweight (BMI ≥ 25) (17.2% vs. 43.9%, P = 0.019) and more lymph vascular space invasion (43.3% vs. 21.1%, P = 0.029). Although no relationship between glucometabolism parameters and MMR status was observed in all enrolled patients, higher SUVmax was observed in the endometrioid type of EC with MMR deficiency (P = 0.047). Additionally, SUVmax related to MMR status was found in EC patients with advanced FIGO stage (P = 0.026) or deep myometrial invasion (P = 0.026). Multivariate Cox regression analysis revealed that lymph node metastasis was independently predictive of PFS, while advanced FIGO stage was an independent predictor of OS. No significant association between MMR status and prognosis was found in EC. CONCLUSION: Higher SUVmax was associated with MMR deficiency in EC patients with endometrioid type, advanced stage, or deep myometrial invasion, which may be useful for predicting the MMR status and thus aiding in determination of immunotherapy for patients with EC.

Invasive mucinous adenocarcinoma of the lung: clinicopathological features, 18F-FDG PET/CT findings, and survival outcomes.

OBJECTIVE: Invasive mucinous adenocarcinoma (IMA) is a rare subtype of lung adenocarcinoma. This study aimed to retrospectively evaluate the clinicopathological features, 18F-FDG PET/CT findings, and prognosis of IMA of the lung, as well as to investigate the associations among these variables, to improve the management of such patients. METHODS: Clinicopathological and 18F-FDG PET/CT characteristics of 72 patients with pathologically confirmed IMA of the lung were retrospectively collected and investigated, and their predictive efficacy on progression-free survival (PFS) was evaluated. RESULTS: The median age of the enrolled 72 patients was 61 years (range, 26-79 years), and the male-to-female ratio was 1:1.25. According to the radiological morphology of IMA, solidary nodule/mass type (n = 59, 81.9%) was the most common, followed by GGO type (n = 8, 11.1%) and pneumonia type (n = 5, 6.9%). Lobulated or spiculated margin and pleural traction were the most common radiological signs. The median SUVmax of IMA lesions was 3.0, ranging from 0.5 to 23.1. Higher SUVmax was observed in IMA with non-GGO type, clinical symptom, advanced stage, lobulated margin, pleural traction or spread through air spaces (STAS) (P < 0.05). Moreover, higher SUVmax was related to larger tumor size in non-pneumonia-type IMA (r = 0.708, P < 0.001). The median PFS was 21.3 months, and the 12-, 24- and 36-month PFS rates were 89.8%, 83.3% and 75.5%, respectively. A poorer PFS was significantly associated with SUVmax ≥ 3, advanced stage and STAS. CONCLUSION: 18F-FDG PET/CT combined with clinicopathological characteristics can aid the diagnosis and prognostic evaluation of lung IMA, which could provide guidance for the appropriate management of such patients.

18F-FDG PET/CT imaging of multiple intrahepatic Epstein-Barr virus-associated smooth muscle tumors in a pediatric patient after heart transplantation.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is an exceedingly rare neoplastic disease with a predisposition in immune-compromised individuals, especially in patients with prior transplantation, human immunodeficiency virus infection, or congenital immunodeficiency. Here, we present imaging findings of EBV-SMT in multiphasic contrast-enhanced computed tomography (CT) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT in a two-and-a-half-year-old boy with prior heart transplantation.

Relationship between 18F-fluorodeoxyglucose PET/computed tomography metabolic parameters and clinicopathology in endometrial cancer.

OBJECTIVE: Endometrial cancer (EC) is the most common invasive gynecological malignancy. This study aimed to retrospectively analyze the relationship between 18F-fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT) parameters and clinicopathological factors in EC patients, and assess whether 18F-FDG PET/CT can be applied for predicting the expressed status of histologic molecular markers. METHODS: Pretreatment clinicopathological characteristics and 18F-FDG PET/CT parameters of maximum standard uptake value (SUVmax), metabolic tumor volume and total lesion glycolysis of primary lesion (MTV-P and TLG-P), and combination of primary lesion and metastases (MTV-C and TLG-C) were retrospectively reviewed in 101 patients with EC. RESULTS: The median age of these 101 patients was 55 years (range, 35-85 years), and 95 patients (94.1%) presented with abnormal vaginal bleeding, 26 patients (25.7%) with elevated serum cancer antigen 125 (CA-125) and 46 patients (45.5%) with increased human epididymis protein 4 (HE4). Sixty-nine cases were at International Federation of Gynecology and Obstetrics (FIGO) stage I, eight at stage II, 20 at stage III, and four at stage IV. FDG uptake was avid in all cases, and the median SUVmax, MTV-P, TLG-P, MTV-C, and TLG-C were 12.9 (range, 2.8-34.2), 8.1 (range, 0.9-547.8), 52.2 (range, 2.5-4420.6), 8.2 (range, 0.9-790.3), and 58.4 (range, 2.5-6972.2), respectively. Estrogen receptor (ER) and progesterone receptor (PR) positive expressions were in 93.1% (94/101) and 90.1% (91/101) patients, respectively. The median Ki-67 index of 101 cases was 40% (range, 0-95%). P53 pattern was tested in 89 patients and 24 cases were mutant type (27.0%). Mesenchymal-epithelial transition factor (c-Met) expression was investigated in 86 patients, and the positivity was in 36 patients (41.9%). Higher PET/CT metabolic parameters were observed in patients with elevated CA-125 and HE4, advanced FIGO stage and higher Ki-67 index (P < 0.05), but had no association with ER/PR expression, P53 pattern, and c-Met expression (P > 0.05). CONCLUSION: FDG uptake in EC was associated with serum CA-125 and HE4, FIGO stage, and Ki-67 index, but no correlations were found between glucose metabolism and ER/PR, P53, and c-Met.

Preoperative prediction of intra-tumoral tertiary lymphoid structures based on CT in hepatocellular cancer.

PURPOSE: Intra-tumoral tertiary lymphoid structures (TLSs) are associated with a favorable prognosis for patients with hepatocellular carcinoma (HCC). We aimed to identify image features related to TLSs and develop a nomogram for preoperative noninvasive prediction of intra-tumoral TLSs. METHODS: This retrospective study enrolled patients with HCC who underwent contrast-enhanced computed tomography before surgery between January 2014 and September 2020. Two radiologists retrospectively and independently reviewed the CT imaging features, and interobserver agreement was assessed. Univariable and multivariable logistic regression analyses were applied to investigate clinical laboratory data and imaging features related to TLSs. A regression-based predictive model and nomogram were constructed using the identified predictors. Nomogram diagnostic performance was assessed with the area under the receiver operating characteristic curve (AUC) and calibration curves, and validated using 5-fold cross-validation. RESULTS: Ninety-three of the 142 HCCs were TLS + HCCs. Multivariable analyses identified intratumor arteries (odds ratio [OR]: 0.23; 95% confidence interval [CI]: 0.07-0.63; p = 0.007), intratumor hemorrhage (OR: 0.08; 95% CI: 0.01-0.50; p = 0.012), positive HBsAg or HCVAB status (OR: 4.52; 95% CI: 1.65-13.29; p = 0.004), platelet count (≥186.5 × 109 /L, OR: 0.38; 95% CI: 0.16-0.86; p = 0.022), and aspartate transaminase level (≥33.2 IU/l, OR: 0.24; 95% CI: 0.09-0.59; p = 0.003) as independent predictors of intra-tumoral TLSs. AUC of the regression-based model was 0.79 (95% CI:0.72-0.86) and average AUC at 5-fold cross-validation was 0.75 (95% CI: 0.71-0.80). CONCLUSIONS: CT-based nomogram is promising for preoperative prediction of intra-tumoral TLS in HCC.

Clinical utility of 18F-FDG PET/CT imaging in patients with pulmonary artery sarcoma.

BACKGROUND: Pulmonary artery sarcoma (PAS) is a rare and fatal malignancy. Due to the lack of specific clinical and radiological features, PAS is always misdiagnosed as pulmonary thromboembolism (PTE). This study aimed to investigate 18F-FDG PET/CT in distinguishing PAS from PTE, and analyze its correlation with clinical and radiological findings and outcome of PAS. METHODS: Clinical, contrast-enhanced CT, and 18F-FDG PET/CT characteristics of 14 patients with PAS and 33 patients with PTE were retrospectively reviewed. The correlation between PET/CT metabolic parameters vs. clinical and CT findings was investigated in patients with PAS. The overall survival (OS) was analyzed in PAS patients. RESULTS: The SUVmax of PAS (median: 8.0, range 3.0-17.2) was significantly higher than PTE (1.8[0.8-3.7]) (P < 0.001), and at a cutoff value of 2.9, the sensitivity and specificity were 100.0% and 93.9%, respectively. Compared with PTE, PAS more frequently occurred in younger population (P = 0.011), involved pulmonary trunk (P < 0.001), and displayed higher enhanced CT (P < 0.001) and ΔCT (enhanced CT compared to non-enhanced CT) (P < 0.001) values. SUVmax of PAS was associated with tumor staging (P = 0.022) and enhanced CT (P = 0.013) and ΔCT (P = 0.005) values. The median OS of PAS patients was 10.5 months, and 12-month and 24-month OS rates were 58.0% and 12.0%, respectively. Only D-dimer level (P = 0.038) and tumor staging (P = 0.019) were associated with OS. CONCLUSIONS: Most PAS displayed high glucometabolism, and SUVmax of 18F-FDG PET/CT was useful in distinguishing PAS from PTE.

A Solitary Spinal Cord Metastasis From Lung Cancer Displayed on 18 F-FDG PET/CT.

ABSTRACT: Chest CT images were acquired in a 79-year-old man to evaluate a right lung mass revealed by chest radiography. The image findings suggested possible pulmonary malignancy. FDG PET/CT was performed for staging, which displayed not only a hypermetabolic mass in the upper lobe of right lung but also increased FDG uptake of the spinal cord at T11 to T12 level. A lesion corresponding to the hypermetabolic region of the spinal cord was revealed by MRI. The intramedullary spinal cord metastasis from lung squamous cell carcinoma was confirmed through the pathological examination after the spinal cord lesion was resected.

OLFM4 depletion sensitizes gallbladder cancer cells to cisplatin through the ARL6IP1/caspase-3 axis.

BACKGROUND: Gallbladder cancer (GBC) is a highly lethal malignancy that carries an extremely poor prognosis due to its chemoresistant nature. Cisplatin (CDDP) is a first-line chemotherapeutic for GBC; however, patients experienced no benefit when treated with CDDP alone. The underlying mechanisms of CDDP resistance in GBC remain largely unknown. METHODS: Agilent mRNA microarray analysis was performed between paired GBC and paracarcinoma to explore differentially expressed genes that might underlie drug resistance. Gene Set Enrichment Analysis (GSEA) was employed to identify key genes mediating CDDP resistance in GBC, and immunohistochemistry was performed to validate protein expression and test correlations with clinicopathological features. In vitro and in vivo functional assays were performed to investigate the proteins' roles in CDDP resistance. RESULTS: Olfactomedin 4 (OLFM4) was differentially expressed between GBC and paracarcinoma and had the highest rank metric score in the GSEA. OLFM4 expression was increasingly upregulated from chronic cholecystitis to GBC in clinical tissue samples, and OLFM4 depletion decreased GBC cell proliferation and invasion. Interestingly, downregulation of OLFM4 reduced ARL6IP1 (antiapoptotic factor) expression and sensitized GBC cells to CDDP both in vitro and in vivo. The evidence indicated that CDDP could significantly increase Bax and Bad expression and activate caspase-3 cascade in OLFM4-depleted GBC cells through ARL6IP1. Clinically, lower OLFM4 expression was associated with good prognosis of GBC patients. CONCLUSIONS: Our results suggest that OLFM4 is an essential gene that contributes to GBC chemoresistance and could serve as a prognostic biomarker for GBC. Importantly, OLFM4 could be a potential chemotherapeutic target.

Autocatalytic biosynthesis of abscisic acid and its synergistic action with auxin to regulate strawberry fruit ripening.

Abscisic acid (ABA) plays a major role in the regulation of strawberry fruit ripening; however, the origin of the ABA signal is largely unknown. Here, we report an autocatalytic mechanism for ABA biosynthesis and its synergistic interaction with the auxin to regulate strawberry fruit ripening. We demonstrate that ABA biosynthesis is self-induced in the achenes, but not in the receptacle, which results its substantial accumulation during ripening. ABA was found to regulate both IAA transport and biosynthesis, thereby modulating IAA content during both early fruit growth and later during ripening. Taken together, these results reveal the origins of the ABA signal and demonstrate the importance of its coordinated action with IAA in the regulation of strawberry fruit development and ripening.

A Method for Assaying of Protein Kinase Activity In Vivo and Its Use in Studies of Signal Transduction in Strawberry Fruit Ripening.

Strawberry (Fragaria × ananassa) fruit ripening is regulated by a complex of cellular signal transduction networks, in which protein kinases are key components. Here, we report a relatively simple method for assaying protein kinase activity in vivo and specifically its application to study the kinase, FaMPK6, signaling in strawberry fruit. Green fluorescent protein (GFP)-tagged FaMPK6 was transiently expressed in strawberry fruit and after stimuli were applied to the fruit it was precipitated using an anti-GFP antibody. The precipitated kinase activity was measured in vitro using 32P-ATP and myelin basic protein (MBP) as substrates. We also report that FaMPK6 is not involved in the abscisic acid (ABA) signaling cascade, which is closely associated with FaMPK6 signaling in other plant species. However, methyl jasmonate (MeJA), low temperature, and high salt treatments were all found to activate FaMPK6. Transient manipulation of FaMPK6 expression was observed to cause significant changes in the expression patterns of 2749 genes, of which 264 were associated with MeJA signaling. The data also suggest a role for FaMPK6 in modulating cell wall metabolism during fruit ripening. Taken together, the presented method is powerful and its use will contribute to a profound exploration to the signaling mechanism of strawberry fruit ripening.

Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration.

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

The Yunnan national medicine Maytenus compound inhibits the proliferation of hepatocellular carcinoma (HCC) by suppressing the activation of the EGFR-PI3K-AKT signaling pathway.

Objective: To investigate the effects of Maytenus compound on the proliferation of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to explore the underlying mechanism. Methods: The half maximal inhibitory concentration (IC50) values of Maytenus compound in HepG2 and BEL-7402 cells were determined by the MTS assay. HepG2 and BEL-7402 cells were treated with different concentrations of Maytenus compound. MTS assays, colony formation assays and cell cycle analyses were performed to clarify the inhibitory effect of Maytenus compound on the proliferation of HepG2 and BEL-7402 cells in vitro. After subcutaneous injection of HepG2 cells, nude mice were randomly divided into a vehicle control group and a drug intervention group, which were intragastrically administered ddH2O or Maytenus compound, respectively. The inhibitory effect of Maytenus compound on the proliferation of HepG2 cells in vivo was analyzed using subcutaneous tumor growth curves, tumor weight, the tumor growth inhibition rate and the immunohistochemical detection of BrdU-labeled cells in S phase. The organ toxicity of Maytenus compound was initially evaluated by comparing the weight difference and organ index of the two groups of nude mice. The main proteins in the EGFR-PI3K-AKT signaling pathway were detected by Western blot after Maytenus compound intervention in vivo and in vitro. Results: Maytenus compound showed favorable antiproliferation activity against HepG2 and BEL-7402 cells with IC50 values of 79.42±11.71 µg/mL and 78.48±8.87 µg/mL, respectively. MTS assays, colony formation assays and cell cycle analyses showed that Maytenus compound at different concentration gradients within the IC50 concentration range significantly suppressed the proliferation of HepG2 and BEL-7402 cells in vitro and inhibited cell cycle progression from G1 to S phase. Additionally, Maytenus compound, at an oral dose of 2.45 g/kg, dramatically inhibited, without obvious organ toxicity, the proliferation of subcutaneous tumors formed by HepG2 cells in nude mice. In addition, the tumor growth inhibition rate for Maytenus compound was 66.94%. Furthermore, Maytenus compound inhibited the proliferation of liver orthotopic transplantation tumors in nude mice. Western blot analysis showed that Maytenus compound significantly downregulated the expression of p-EGFR, p-PI3K, and p-AKT and upregulated the expression of p-FOXO3a, p27, and p21 in vivo and in vitro. Conclusion: Maytenus compound significantly inhibited the proliferation of HCC cells in vitro and in vivo. The downregulation of the EGFR-PI3K-AKT signaling pathway and subsequent inhibition of cell cycle progression from G1 to S phase is one of the possible mechanisms. Maytenus compound has a high tumor growth inhibition rate and has no obvious organ toxicity, which may make it a potential anti-HCC drug, but the results from this study need to be confirmed by further clinical trials in HCC patients.

An effector-reporter system to study cellular signal transduction in strawberry fruit (Fragaria ananassa).

An effector-reporter system is a powerful tool used to study cellular signal transduction, but this technique has been traditionally used in protoplasts. A similar system to study cellular signal transduction in fruits has not yet been established. In this study, we aimed to establish an effector-reporter system for strawberry fruit, a model nonclimacteric fruit. We first investigated the characteristics of transient gene expression in strawberry fruits and found marked variation in gene expression levels among individual fruits, and this variation has complicated the establishment of a technical system. To overcome this difficulty, we investigated a sampling strategy based on a statistical analysis of the activity pattern of four different reporters (GUS, GFP, FLuc, and RLuc) among individual fruits and combinations of pairs of reporters (GUS/GFP and RLuc/FLuc). Based on an optimized sampling strategy, we finally established a step-by step protocol for the effector/reporter assay. Using FaMYB10 and FaWRKY71 as the effectors and GUS driven by the FaCHS promoter as the reporter, we demonstrated that this effector/reporter system was practical and reliable. This effector/reporter technique will contribute to an in-depth exploration of the signaling mechanism for the regulation of strawberry fruit ripening.

FAM136A immunoreactivity is associated with nodal involvement and survival in lung adenocarcinoma in a Chinese case series.

Lung cancer patients with lymph node metastasis usually had short overall survival and occurred distant metastases at the early stage. However, some of these people did have more prolonged survival. The underlying reason is still unclear. In this study, we found a novel molecule, family with sequence similarity 136, member A gene (FAM136A). First, we performed immunohistochemistry for FAM136A in 177 lung carcinoma tissues. Second, we carried out in vitro studies by using A549 and PC-9. We detected FAM136A immunoreactivity in 79 out of 177 (44.6%) lung carcinoma tissues, and the FAM136A status was significantly associated with tumor T stage, lymph node metastasis, and the Tumor-Node-Metastasis (TNM) staging system in these cases. Importantly, it was significantly associated with the overall survival of the patients with lymph node metastasis, especially FAM136A positive patients, who had worse outcomes. Subsequent in vitro experiments revealed that the proliferation activity and migration property decreased both A549 and PC-9 lung carcinoma cells transfected with siRNA-FAM136A, and apoptosis reduced. Meanwhile, the expression of CDK4 and CDK6 decreased. FAM136A status would be a potent, worse prognostic factor in lung cancer patients with lymph node metastasis. It would play a vital role in the proliferation, apoptosis, and migration properties of A549 and PC-9. In the future, We will focus on the uncovered signal mechanism between FAM136A and lung cancer.

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma.

BACKGROUND: In clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin's Lymphoma (cHL). METHODS: In order to understand the applicable population of multiple CAR T-cell therapy, we examined the expression of CD19, CD20, and CD30 by immunohistochemistry (IHC) in 38 paraffin-embedded specimens of cHL. In the past two years, we found only one patient with cHL who is eligible for combined anti-CD19 and CD30 CAR T-cell treatment. This patient's baseline characteristics were prone to severe adverse events. We treated this patient with low doses and multiple infusions of anti-CD19 and CD30 CAR T-cell. RESULTS: The positive expression of CD19+ + CD30+ in Reed-Sternberg (RS) cells is approximately 5.2% (2/38). The patient we treated with combined anti-CD19 and CD30 CAR T-cell did not experience severe adverse events related to CAR T-cell therapy and received long term progression-free survival (PFS). CONCLUSION: For high risk r/r cHL patients, low doses of CAR T-cell used over different days at different times might be safe and effective. More clinical trials are warranted for CD19 and CD30 CAR T-cell combination therapy.

Knockdown of microsomal glutathione S-transferase 1 inhibits lung adenocarcinoma cell proliferation and induces apoptosis.

BACKGROUND: Lung cancer has been the most common cancer worldwide. Microsomal glutathione S-transferase 1 (MGST1) has been reported to play vital roles in oxidative stress, tumor occurrence and drug resistance. However, the biological function and molecular mechanism of MGST1 in lung adenocarcinoma (LUAD) has not yet been elucidated. METHODS: The expression of MGST1 in LUAD tissues and cell lines was evaluated by immunohistochemistry and western blotting, respectively. MGST1 was knocked down by shRNA lentivirus. Cell proliferation was evaluated by MTS, colony formation and EdU assays. Apoptosis was detected by flow cytometry. The potential molecules involved in cell proliferation and apoptosis were examined by western blotting. Finally, the effect of MGST1 on tumor growth in vivo was evaluated in a nude mouse xenograft model. RESULTS: TCGA database analysis and immunohistochemistry demonstrated that MGST1 was highly expressed in LUAD tissues. MGST1 expression in LUAD was correlated with AJCC stage and poor overall survival of patients. MGST1 knockdown significantly inhibited LUAD cell proliferation and induced apoptosis. Mechanistic analyses revealed that MGST1 knockdown might inhibit cell proliferation by inactivating the AKT/GSK-3ß pathway signaling and promote cell apoptosis by regulating the mitochondrial apoptosis pathway related proteins. Moreover, knockdown of MGST1 suppressed tumor growth in vivo. CONCLUSIONS: MGST1 plays an important role in LUAD tumorigenesis and might serve as a potential prognostic factor and therapeutic target in LUAD.

Knockdown of STIM1 expression inhibits non-small-cell lung cancer cell proliferation in vitro and in nude mouse xenografts.

Stromal interaction molecule 1 (STIM1) is a calcium-sensing protein localized in the membrane of the endoplasmic reticulum. The expression of STIM1 has been shown to be closely associated with cell proliferation. The aim of the present study was to investigate the role of STIM1 in the regulation of cancer progression and its clinical relevance. The data demonstrated that the expression of the STIM1 was significantly higher in non-small-cell lung cancer (NSCLC) tissues than in benign lesions and was associated with advanced NSCLC T stage. Knockdown of STIM1 expression in NSCLC cell lines A549 and SK-MES-1 significantly inhibited cell proliferation and induces A549 and SK-MES-1 cell arrest at the G2/M and S phases of the cell cycle. Western blotting showed that the expression of cyclin-dependent kinase (CDK) 1 and CDK2 were reduced while knockdown of STIM1 expression. Furthermore, knockdown of STIM1 in NSCLC cells significantly reduced the levels of xenograft tumor growth in nude mice. These data indicate that aberrant expression of the STIM1 protein may contribute to NSCLC progression. Future studies should focus on targeting STIM1 as a novel strategy for NSCLC therapy.

HDGF and PRKCA upregulation is associated with a poor prognosis in patients with lung adenocarcinoma.

Lung adenocarcinoma is the most common histologic subtype of lung cancer. The aim of the present study was to assess the expression of hepatoma-derived growth factor (HDGF) and protein kinase Cα (PRKCA) in lung adenocarcinoma (LADC), and to determine the association between the combined expression of these two proteins and clinicopathological characteristics of patients with LADC. The expression of HDGF and PRKCA mRNA was assessed by GEO database analysis, and HDGF and PRKCA protein levels were examined by immunohistochemistry using a tissue microarray. High HDGF and PRKCA expression was observed in LADC tissue compared to normal samples, and increased HDGF and PRKCA expression was associated with AJCC clinical stage, tumor classification, node classification, and lymph node metastasis. GEO database analysis revealed no significant differences between HDGF mRNA and PRKCA mRNA in LADC tissue. However, high PRKCA protein expression was associated with high HDGF protein expression, and patients with high HDGF and PRKCA expression exhibited poorer overall survival rates than patients with low expression levels of the two proteins. The results of the present study suggest that upregulation of both HDGF and PRKCA may be an unfavourable factor for lung adenocarcinoma progression.

Curcumin inhibits cell proliferation and migration in NSCLC through a synergistic effect on the TLR4/MyD88 and EGFR pathways.

Despite the increasing number of available therapeutic methods, the prognosis of non­small cell lung cancer (NSCLC) remains poor. Furthermore, side effects are an important limiting factor in the treatment of NSCLC. Therefore, developing an efficacious, safe, affordable and easily accessible chemotherapeutic agent is necessary for NSCLC treatment. As a natural chemical produced by Zingiberaceae plants, curcumin exerts distinct antitumor effects on several tumor types. In the present study, curcumin was observed to inhibit not only cell proliferation and cell cycle transition, but also cell migration in NSCLC, as determined by a series of experiments (such as MTS assay, colony formation assay, flow cytometric analysis, Transwell migration assay and western blotting). Mechanistically, curcumin induced G2/M phase arrest by controlling cell cycle­ and epithelial­mesenchymal transition (EMT)­related checkpoints. Furthermore, curcumin significantly inhibited the expression of Toll­like receptor 4 (TLR4)/MyD88 and EGFR in a dose­ and time­dependent manner. Conversely, EGF reversed the inhibitory action of curcumin on TLR4/MyD88. In clinical specimens, TLR4 and MyD88 were highly expressed in NSCLC tissues, and a significant positive association was observed between TLR4 and MyD88 expression. These data suggested that curcumin may control the EGFR and TLR4/MyD88 pathways to synergistically downregulate downstream cell cycle­ and EMT­related regulators, in order to block cell proliferation and metastasis in NSCLC. These findings provide evidence for the clinical application of curcumin.

Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis.

Tumor-infiltrating lymphocytes (TILs) are associated with prognosis in various tumors. However, it remains controversial whether the presence of TILs is related to an improved prognosis in melanoma. This meta-analysis confirmed the favorable prognostic role of the CD3+, CD4+, CD8+, FOXP3+, and CD20+ TILs in the overall survival of melanoma patients and found an association between the TILs present and improved overall survival. Additionally, subgroup analysis demonstrated that brisk TILs were obviously associated with OS, RFS and DSS/MSS. Thus, TILs may be a predictive biomarker in melanoma. This analysis will provide more insight into the study of TILs and predictive biomarker.