Type B thymomas in patients with myasthenia gravis display a distinctive pattern of αß TCR and IL-7 receptor α expression on CD4+CD8+ thymocytes.

Thymoma is closely associated with myasthenia gravis (MG). However, due to the heterogeneity of thymoma and the intricate pathogenesis of MG, it remains unclear why some patients with thymoma develop MG and others do not. In this study, we conducted a comparative phenotype analysis of thymocytes in type B thymomas in patients with MG (MG (+) thymomas) and without MG (MG (-) thymomas) via fluorescence-activated cell sorting (FACS). Our results show that the developmental stages defined by the expression of CD3, CD4, and CD8 were largely maintained in both MG (+) and MG (-) thymomas, with CD4+CD8+ cells constituting the majority of thymocytes in type B thymoma, and no significant difference between this cell population was observed in MG (+) and MG (-) thymomas.We discovered that CD4+CD8+ thymocytes in MG (+) thymomas expressed low levels of αß TCR and high levels of IL-7 receptor α (IL-7Rα), whereas in MG (-) thymomas, CD4+CD8+ thymocytes exhibited the opposite pattern of αß TCR and IL-7Rα expression. These results suggest that the positive and negative selection processes of CD4+CD8+ thymocytes might differ between MG (+) thymomas and MG (-) thymomas. The expression of the Helios transcription factor is induced during negative selection and marks a group of T cells that have undergone negative selection and are likely to be deleted due to strong TCR binding with self-peptides/MHC ligands. We observed that the percentage of Helios-positive CD4SP T cells was greater in MG (-) than in MG (+) thymomas. Thus, the differentially regulated selection process of CD4+CD8+ thymocytes, which involves TCR and IL-7/IL-7Rα signaling, is associated with the presence of MG in type B thymomas.

"Low-age, low-frequency" lung cancer screening strategies maybe adaptable to the situation in China.

BACKGROUND: The object was to compare changes in patients undergoing lung surgery before and after COVID-19 outbreak, and to explore the impact of COVID-19 on lung surgery and its coping strategies. METHOD: A retrospective review of patients undergoing thoracic surgery at a single institution was conducted. Group A included patients treated between January 23, 2019, and January 23, 2020, while Group B included patients treated between June 1, 2020, and June 1, 2021, at our center. We compared the reasons of seeking medical treatment, the general characteristics of patients, imaging features, pathological features, surgical methods and postoperative recovery. RESULT: Compared to Group A, the number of patients with pulmonary nodules screened by routine check-up increased in Group B (57.6% vs 46.9%, p < 0.05). Female patient increased (55.2%vs 44.7%). Patient without smoking history or with family history of lung cancer increased (70.7% vs 60.7%) (10.1%vs 7.8%). Early stage lung cancer increased. Lobectomy decreased (53.4% vs 64.1%). Segmental resection increased (33.3% vs 12.7%). Patients without postoperative comorbidities increased (96.1%vs 85.7%). In the case of patients with Ground Glass Opacity(GGO), their age was comparatively lower (52 ± 9.9 vs. 55 ± 10.7), the female patients increased, patient without smoking history, tumor history, family history of tumor increased, small GGO increased. Lobectomy decreased (35.2% vs 49.7%). Segmental resection increased (49.6% vs 21.2%). Patients without postoperative comorbidities increased (96.5% vs 87.4%). CONCLUSION: Since COVID-19 outbreak, more young, non-smoking, female lung cancers, more Ground Glass Opacity, none high risk patients have been detected through screening, suggesting that our current screening criteria for lung cancer may need to be revised. Higher requirements, including the selection of the timing of nodular surgery, surgical methods were put forward for thoracic surgeons' skills.

Case report: Drainage tube penetrating anastomosis as a rare cause for long-term nonunion of esophagogastric anastomosis in neck.

Anastomotic leakage is a life-threatening complication for esophageal cancer patients who received McKeown esophagectomy. Cervical drainage tube penetrating anastomosis is a rare but noteworthy cause of long-term nonunion of esophagogastric anastomosis. Here we reported two cases of esophageal cancer patients who received McKeown esophagectomy. The first case acquired the anastomotic leakage on postoperative day (POD) 7, and lasted for 56 days. The cervical drainage tube was removed at POD 38, and the leakage healed in 25 days. The second case acquired the anastomotic leakage on POD 8 and lasted for 95 days. The cervical drainage tube was removed at POD 57, and the leakage healed in 46 days. The two cases demonstrated the duration-prolonging effect of drainage tube penetrating anastomosis, which should not be overlooked in clinical practice. We suggested paying attention to the duration of leakage, the drainage fluids amounts and characteristics, and the imaging manifestations to help diagnose. If the cervical drainage tube penetrated the anastomosis, the tube should be eliminated as soon.

Multi-omics consensus portfolio to refine the classification of lung adenocarcinoma with prognostic stratification, tumor microenvironment, and unique sensitivity to first-line therapies.

Background: Molecular classification of lung adenocarcinoma (LUAD) based on transcriptomic features has been widely studied. The complementarity of data obtained from multilayer molecular biology could help the LUAD classification via combining multi-omics information. Methods: We successfully divided samples from the The Cancer Genome Atlas (TCGA) (n=437) into four subtypes (CS1, CS2, CS3 and CS4) by 10 comprehensive multi-omics clustering methods in the "movics" R package. Meanwhile, external validation sets from different sequencing technologies proved the robustness of the grouping model. The relationship between subtypes, prognosis, molecular features, tumor microenvironment and response to first-line therapy was further analyzed. Next we used univariate Cox regression analysis and Lasso regression analysis to explore the application of biomarkers in clinical prognosis and constructed a prognostic model. Results: CS1 showed the worst overall survival (OS) among all four clusters, possibly related to its poor immune infiltration, higher tumor mutation and worse chromosomal stability. Patients in different subtypes differed significantly in cancer stem cell characteristics, activation of cancer-related pathways, sensitivity to chemotherapy and immunotherapy. The prognostic model showed good predictive performance. The 1-, 2- and 3-year areas under the curve of risk score were 0.779, 0.742 and 0.678, respectively. Seven genes (DKK1, TSPAN7, ID1, DLGAP5, HHIPL2, CD40 and SEMA3C) used to build the model may be potential therapeutic targets for LUAD. Conclusions: Four LUAD subtypes with different molecular characteristics and clinical implications were identified successfully through bioinformatic analysis. Our results may contribute to precision medicine and inform the development of rational clinical strategies for targeted and immune therapies.

Simultaneous resection of coexisting pulmonary and mediastinal lesions by video-assisted thoracic surgery: a case-series study.

BACKGROUND: With the growing number of patients with coexisting pulmonary and mediastinal lesions detected, reports about simultaneous video-assisted thoracic surgery (VATS) for these concurrent diseases are still rare. To further explore the safety and effectiveness of simultaneous resection of pulmonary and mediastinal lesions by uniportal or biportal VATS, we retrospectively analyzed the clinical data of the largest series of cases to date. METHODS: From July 2018 to July 2021, all patients whose pulmonary lesions and mediastinal tumors were resected simultaneously in our institution were retrospectively reviewed. Their demographic and clinical data were collected and analyzed. RESULTS: A total of 54 patients were enrolled, of whom 44 underwent unilateral uniportal VATS, 3 underwent bilateral uniportal VATS and 7 underwent unilateral biportal VATS. Seven cases were converted to thoracotomy during surgery. For the remaining 47 patients with various demographic and clinical characteristics, most of the operations were completed within 3 h (n = 33, 70.2%) with blood loss of no more than 100 mL (n = 43, 91.5%). The duration of chest tube drainage was 5.66 ± 3.34 days, and the average daily volume was 196.90 ± 122.31 mL. Four cases of postoperative complications occurred during hospitalization. The length of postoperative hospital stay was 8.60 ± 3.63 days. No severe complications or deaths were observed during follow-up. CONCLUSIONS: Uniportal and biportal VATS are safe and effective for simultaneous resection of selected coexisting pulmonary and mediastinal lesions, but the indications and operational details need more evaluation.

A new minimally invasive technique for correction of pectus carinatum.

BACKGROUND: The Abramson technique for the correction of pectus carinatum (PC) is commonly performed worldwide. However, the postoperative complications of this technique related to bar fixation, including wire breakage and bar displacement, are relatively high. In this study, a new minimally invasive technique for correction of PC is described, in which the pectus bar is secured by bilateral selected ribs, and for which no special fixation to the rib is needed. METHODS: The procedure was performed by placing the pectus bar subcutaneously over the sternum with both ends of the bar passing through the intercostal space of the selected rib at the anterior axillary line. The protruding sternum was depressed by the bar positioned in this 2 intra- and 2 extra-thorax manners. Between October 2011 and September 2019, 42 patients with PC underwent this procedure. RESULTS: Satisfactory cosmetic results were obtained in all the patients. The mean operation time was 87.14 min, and the mean postoperative stay was 4.05 days. Wound infection occurred in 3 patients, 2 were cured by antibiotics, and 1 received bar removal 4 months after the initial operation due to the exposure of the implant resulting from uncontrolled infection. Mild pneumothorax was found in 3 patients and cured by conservative treatment. One patient suffered from hydropneumothorax, which was treated with chest drainage. The bars were removed at a mean duration of 24.4 months since primary repair in 20 patients without recurrence. CONCLUSIONS: This new technique for minimally invasive correction of PC deformity is a safe and feasible procedure yielding good results and minimal complications.

LLL12B, a small molecule STAT3 inhibitor, induces growth arrest, apoptosis, and enhances cisplatin-mediated cytotoxicity in medulloblastoma cells.

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor and an oncogene product, which plays a pivotal role in tumor progression. Therefore, targeting persistent STAT3 signaling directly is an attractive anticancer strategy. The aim of this study is to test the efficacy of a novel STAT3 small molecule inhibitor, LLL12B, in suppressing medulloblastoma cells in vitro and tumor growth in vivo. LLL12B selectively inhibited the induction of STAT3 phosphorylation by interleukin-6 but not induction of STAT1 phosphorylation by INF-γ. LLL12B also induced apoptosis in human medulloblastoma cells. In addition, LLL12B exhibited good oral bioavailability in vivo and potent suppressive activity in tumor growth of medulloblastoma cells in vivo. Besides, combining LLL12B with cisplatin showed greater inhibition of cell viability and tumorsphere formation as well as induction of apoptosis comparing to single agent treatment in medulloblastoma cells. Furthermore, LLL12B and cisplatin combination exhibited greater suppression of medulloblastoma tumor growth than monotherapy in vivo. The present study supported that LLL12B is a novel therapeutic agent for medulloblastoma and the combination of LLL12B with a chemotherapeutic agent cisplatin may be an effective approach for medulloblastoma therapy.

A small molecule STAT3 inhibitor, LLL12, enhances cisplatin­ and paclitaxel­mediated inhibition of cell growth and migration in human ovarian cancer cells.

Ovarian cancer is one of the most lethal cancer types in American women. The platinum agent cisplatin, and/or paclitaxel, remains the first­line chemotherapy for ovarian cancer, but the treatment success is severely limited by chemoresistance. As previously reported, persistent STAT3 signaling is associated with resistance to cisplatin and paclitaxel. To investigate whether the STAT3 small molecule inhibitor LLL12 can enhance the treatment effect of cisplatin and paclitaxel in ovarian cancer cells, A2780, SKOV3, CAOV­3 and OVCAR5 cells were treated with LLL12, cisplatin and paclitaxel, alone or combination, and cell viability, cell migration, cell growth and protein expression levels were then evaluated. It was found that, for all four human ovarian cancer cell lines, STAT3 phosphorylation was significantly inhibited by LLL12. The combined treatment of LLL12 with paclitaxel or LLL12 with cisplatin exerted significantly greater inhibition of cell viability, cell migration and cell growth than did monotherapy. In addition, LLL12 and cisplatin in combination, or the three drugs in combination, also led to greater inhibition of cell viability and cell migration than combined cisplatin and paclitaxel treatment, a standard treatment for ovarian cancer. The present results demonstrated that the STAT3 small molecule inhibitor LLL12 is a potent inhibitor of STAT3 phosphorylation, cell viability and migration in human ovarian cancer cells. Combining LLL12 with cisplatin or paclitaxel may be a viable therapeutic approach in the treatment of patients with ovarian cancer exhibiting persistent STAT3 signaling.

LLY17, a novel small molecule STAT3 inhibitor induces apoptosis and suppresses cell migration and tumor growth in triple-negative breast cancer.

PURPOSE: Persistent STAT3 signaling is frequently detected in many cancer types including triple-negative breast cancer, and thus could potentially serve as a viable therapeutic target. We have designed a novel non-peptide compound LLY17 targeting STAT3 using Advanced Multiple Ligand Simultaneous Docking (AMLSD) methods. However, the efficacy of LLY17 has not been evaluated extensively in human and murine triple-negative breast cancer cells. In this study, we tested LLY17 in multiple human and murine triple-negative breast cancer cell lines. METHODS: Human triple-negative breast cancer MDA-MB-468, MDA-MB-231, SUM159, and BT-549 cells, and murine triple-negative breast cancer 4T1 cells were used to study the inhibition effects of LLY17. The inhibition of STAT3 activation of LLY17 was investigated using western blot analysis. Cell viability, apoptosis and migration assays were carried out by MTT assay, Caspase-3/7 assay and wound healing assay, respectively. A mammary fat pad syngeneic mouse model was used to evaluate the antitumor effect of LLY17 in vivo. RESULTS: LLY17 inhibited IL-6-mediated induction of STAT3 phosphorylation but had no effect on IFN-γ-induced STAT1 phosphorylation or EGF-induced ERK phosphorylation. LLY17 inhibited STAT3 phosphorylation and induced apoptosis in human and murine triple-negative breast cancer cells but exhibited minimal toxicity toward Luminal A subtype breast cancer MCF-7 cells. RNAi attenuation experiments supported the requirement of STAT3 for LLY17-mediated inhibition of cell viability in triple-negative breast cancer cells. In addition, LLY17 inhibited cell migration of human and murine triple-negative breast cancer cells. Furthermore, LLY17 suppressed tumor growth and STAT3 phosphorylation of triple-negative breast cancer cells in a mammary fat pad syngeneic mouse model in vivo. CONCLUSIONS: Together, our findings suggest that targeting persistent STAT3 signaling by novel small molecule LLY17 may be a potential approach for the therapy of triple-negative breast cancer.

Bazedoxifene is a novel IL-6/GP130 inhibitor for treating triple-negative breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has been ranked as one of the devastating malignancy worldwide. Its disease progression and treatment obstacle is associated with the negligible expression of estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-). Due to a lack of growth hormone receptors, TNBC is desperately demanding effective therapeutic regimens. A growing body of evidence indicated that glycoprotein 130 kDa (GP130), the pivotal mediator involved in interleukin 6 (IL-6) and signal transducer and activator of transcription 3 (STAT3) signaling pathways, is strongly correlated with tumor progression. Therefore, GP130 could become a novel target for treating TNBC. In our earlier studies, we demonstrated bazedoxifene as being a novel GP130 inhibitor. METHODS: In the current report, anti-tumor effect of bazedoxifene on TNBC was further evaluated in TNBC cell lines SUM159, MDA-MB-231, and MDA-MB-468. We assessed anti-TNBC potency of bazedoxifene by carrying out various analysis encompassing western blot, cell proliferation, cell migration, colony formation, and growth of tumors in the xenograft mice. RESULTS: Our findings demonstrated that bazedoxifene not only decreased the expression of P-STAT3, IL-6/GP130-mediated downstream target genes P-AKT and P-ERK, but also blocked mitogen effects stimulated by IL-6, including cell viability, and overall cell survive, proliferation as well as cell migration. Likewise in laboratory animal model, tumor growth in mice was remarkably suppressed by bazedoxifene via an oral administration route. Combinational treatment of bazedoxifene plus the conventional chemotherapeutic agent, paclitaxel, synergistically impeded cell viability, colony formation, and cell migration far more significantly than the one from single-drug alone. CONCLUSIONS: Taken together, our data suggest that bazedoxifene may be developed as a promising small molecular therapeutic agent for eradicating TNBC intrinsically associated with constitutively active IL-6/GP130/STAT3 signaling cascade.

Combined bazedoxifene and paclitaxel treatments inhibit cell viability, cell migration, colony formation, and tumor growth and induce apoptosis in breast cancer.

Breast cancer, especially triple-negative breast cancer (TNBC), has limited treatment options. We repurposed the FDA-approved drug bazedoxifene as a novel inhibitor of interleukin 6/glycoprotein 130 signaling. In this study, we investigated the inhibitory effects of bazedoxifene alone or in combination with paclitaxel on several estrogen receptor positive and TNBC cells. Bazedoxifene inhibited the cell viability of these cells, as well as tumor growth of TNBC cells in a xenograft tumor model. Furthermore, bazedoxifene combined with paclitaxel exhibited more potent inhibition of cell viability, colony formation, and cell migration and induced more apoptosis in vitro, and generated stronger inhibition of tumor growth of TNBC in vivo than either drug alone. Western blotting showed that bazedoxifene inhibited estrogen receptor positive breast cancer cells by suppressing the expression of estrogen receptor, Cyclin D1, p-P70S6K, Survivin, c-Myc, and Bcl-2, and bazedoxifene inhibited TNBC cells by inhibiting the expression of phosphorylated STAT3 (Tyr705), Cyclin D1, p-P70S6K, c-Myc, p-AKT (Ser473) and p-ERK 1/2 (T202/Y 204) without changing the expression of total STAT3. When combined with paclitaxel, bazedoxifene may be a potential small molecule for the treatment of both estrogen receptor positive and triple-negative breast cancer.

Retraction Note: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma.

The authors have retracted the article [Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma, Cell Death & Disease volume 7, page e2388 (2016), doi 10.1038/cddis.2016.260] because it has recently come to their attention that the A549 cells used in this research were contaminated with Hela cells, which may have altered the outcome of their experiment. The conclusions of this article are therefore unreliable. All authors agree to this retraction.

Modified McKeown procedure with uniportal thoracoscope for upper or middle esophageal cancer: initial experience and preliminary results.

BACKGROUND: Uniportal video-assisted thoracic surgery (VATS) resections are of increasing interest in many thoracic surgery departments. With each experience in VATS lobectomy, we have incrementally improved the less invasive techniques in esophagectomy. Here, we report the preliminary results and feasibility of a modified McKeown procedure with uniportal thoracoscopy for upper or middle esophageal cancer in our institution. METHODS: Between March 2015 and May 2016, modified uniportal McKeown procedure with uniportal thoracoscopy for upper or middle esophageal cancer was attempted in 44 patients in our institution. RESULTS: Of the patients treated with uniportal thoracoscopy and laparoscopy, no patients were converted to open procedures, and all had a complete resection. The mean operative time was 408±34 min (range, 394-495 min). The mean thoracic operation was 163±16 min (range, 135-199 min). The mean blood loss was 245±102 mL (range, 100-450 mL). The mean number of lymph nodes resected was 24 (range, 14-36). The mean ventilator usage of the patients after surgery was 0.3±0.6 days, and the mean intensive care stay was 1.6 days (range, 1 to 7 days). The mean hospital stay was 11.8 days (range, 7 to 22 days). Major complications developed in 2 patients, both of whom had to undergo tracheotomy due to respiratory failure. No patients died of complications postoperatively, and none had clinically significant anastomotic leaks. CONCLUSIONS: Modified McKeown minimally invasive esophagectomy (MIE) with uniportal thoracoscopy seems to be a feasible option for patients with upper or middle esophageal cancer. Larger studies with longer follow-up are needed to further investigate this approach.

Blocking Interleukin-6 and Interleukin-8 Signaling Inhibits Cell Viability, Colony-forming Activity, and Cell Migration in Human Triple-negative Breast Cancer and Pancreatic Cancer Cells.

BACKGROUND/AIM: Interleukin-6 (IL-6) and interleukin-8 (IL-8) play important roles in the progression of triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC). This is the first experiment to combine small molecules targeting these two signaling pathways to treat TNBC and PDAC cells. MATERIALS AND METHODS: Cell viability, colony formation and cell migration assays were conducted when TNBC or PDAC cells were treated with bazedoxifene (targeting IL-6) or reparixin/SCH527123 (targeting IL-8) or their combination. RESULTS: The combined treatment had a more potent inhibition of cell viability, colony formation and cell migration than monotherapy in TNBC and PDAC cells. The results also showed that the combination of bazedoxifene with SCH527123 seemed to be more effective than that with reparixin in inhibiting cell viability and colony formation of TNBC. CONCLUSION: Novel drug combinations of bazedoxifene and reparixin, as well as bazedoxifene and SCH527123 may provide more effective treatments for TNBC and PDAC.

Correction to: Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma.

Following publication of their article, the authors noticed that there were minor errors in Figs. 3, 7 and S5. The errors had no effect on the scientific content or conclusions. The rectified figures are given below.

Inhibition of interleukin 8/C­X-C chemokine receptor 1,/2 signaling reduces malignant features in human pancreatic cancer cells.

Interactions between interleukin (IL)-8 and its receptors, C­X-C chemokine receptor 1, (CXCR1) and CXCR2 serve crucial roles in increasing cancer progression. Inhibition of this signaling pathway has yielded promising results in a number of human cancers, including breast, melanoma and colon. However, the effects of CXCR1/2 antagonist treatment on pancreatic cancer remain unclear. The present study aimed to demonstrate that treatment with the clinical grade CXCR1/2 antagonist, reparixin, or the newly discovered CXCR1/2 antagonist, SCH527123, may result in a reduction of the malignant features associated with this lethal cancer. The effects of reparixin or SCH527123 exposure on human pancreatic cancer cell lines BxPC­3, HPAC, Capan­1, MIA PaCa­2, and AsPC­1 were examined in regard to cell proliferation, cell viability, colony formation and migration. The effects of CXCR1/2 inhibition on the protein expression of well-known downstream effectors, including phosphorylated (p)-signal transducer and activator of transcription 3 (STAT3), p­RAC­α serine/threonine-protein kinase (p­AKT), p­extracellular signal-regulated kinase (p­ERK1/2) and p­ribosomal protein S6 (p­S6), were assessed by western blotting assays. The effects of IL­8 signaling on the proliferative activities intrinsic to the human pancreatic cancer cell lines Capan­1, AsPC­1 and HPAC were examined by bromodeoxyuridine assay. Treatment with either reparixin or SCH527123 yielded dose-dependent growth suppressive effects on HPAC, Capan­1 and AsPC­1 cells that may have otherwise undergone robust proliferation upon IL­8 stimulation. In addition, reparixin or SCH527123 treatment inhibited CXCR1/2-mediated signal transduction, as demonstrated by the decreased phosphorylation levels of effector molecules STAT3, AKT, ERK and S6 that are downstream of the IL­8/CXCR1/2 signaling cascade in HPAC cells. These data were in close agreement with the reduced cell migration and colony formation. Results from the present study suggested that reparixin and SCH527123 may be promising therapeutic agents for the treatment of pancreatic cancer by inhibiting the IL­8/CXCR1/2 signaling cascade.

IFN-γ-mediated inhibition of lung cancer correlates with PD-L1 expression and is regulated by PI3K-AKT signaling.

IFN-γ plays a crucial role in anti-tumor responses and also induces expression of PD-L1, a well-established inhibitor of anti-tumor immune function. Understanding how molecular signaling regulates the function of IFN-γ might improve its anti-tumor efficacy. Here, we show that the tumor expression of IFN-γ expression alone has no significant prognostic value in patients with locally advanced lung adenocarcinoma. Surprisingly, patients with tumors expressing both IFN-γ and PD-L1 have the best prognosis compared to those with tumors expressing IFN-γ or PD-L1 alone. Transcriptome analysis demonstrated that tumor tissues expressing IFN-γ display gene expression associated with suppressed cell cycle progression and expansion. Unexpectedly this profile was observed in PD-L1+ but not PD-L1- tumors. The current concept is that PD-L1 functions as a shield protecting tumor cells from cytolytic T cell (CTL)-mediated anti-tumor progression. However, our data indicate that PD-L1 expression in the presence of IFN-γ might serve as biomarker for the sensitivity of tumors to the inhibitory effect of IFN-γ. Mechanistic analysis revealed that in lung adenocarcinoma cells IFN-γ-induced activation of JAK2-STAT1 and PI3K-AKT pathways. The activation of JAK2-STAT1 is responsible for the anti-proliferative effect of IFN-γ. Inhibition of PI3K downregulated PD-L1 expression and enhanced the anti-proliferative effect of IFN-γ, suggesting that blockade of PI3K might maximize the IFN-γ-mediated anti-tumor effect. Our findings provide evidence for crosstalk between JAK2-STAT1 and PI3K-AKT pathways in response to IFN-γ in lung adenocarcinoma and have implications for the design of combinatorial targeted therapy and immunotherapy for the treatment of lung adenocarcinoma.

Estrogen receptor ß1 activation accelerates resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR­TKIs) have revolutionized the treatment of patients with advanced EGFR-mutant NSCLC. However, drug resistance eventually develops in the majority of patients despite an excellent initial response. The present study aimed to investigate the mechanism of acquired resistance to EGFR-TKIs and to explore strategies to overcome the resistance to EGFR-TKIs from a gender perspective. PC9 and Hcc827 cell lines, sensitized to EGFR-TKI, and secondary TKI-resistant PC9-ER (erlotinib resistant) and Hcc827-ER cell lines were evaluated for the expression of ERß1. The proliferative ability of both cell lines was analyzed after transfection of siRNA-ERß1 using Cell Counting Kit-8 and colony formation assays. Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Akt activation were detected. The co-inhibition efficiency of erlotinib and fulvestrant was analyzed in PC9-ER xenografts. The expression of ERß1 was investigated in tumor tissues of EGFR-TKI-treated patients, and its correlation with clinicopathological factors and progression-free survival (PFS) was assessed. The expression of ERß1 was upregulated secondary to EGFR-TKIs in PC9 and Hcc827 cell lines, with ß-estradiol dependence. Both PC9-ER and Hcc827-ER cell lines were re-sensitized to erlotinib after downregulation of the expression of ERß1. ERK1/2 and Akt pathways were activated following the silencing of the expression of ERß1 in PC9-ER and Hcc827 cell lines. The co-treatment of erlotinib and fulvestrant exhibited better growth inhibitory efficiency compared with the treatment of each agent alone in PC9-ER-derived xenografts. Primary NSCLC samples of 53 patients treated with EGFR-TKIs were analyzed. ERß1 was highly expressed, and the strong expression of cytoplasmic ERß1 was related to a shorter PFS. In conclusion, ERß1 was activated in EGFR-TKI secondary resistance. The downregulation of ERß1 sensitized the cells to EGFR-TKIs. ERß1 may be a key molecule in EGFR-TKI therapy. In addition, anti-ERß1 treatment may reverse TKI resistance.

Modular Uniportal Video-Assisted Thoracoscopic Lobectomy and Lymphadenectomy: A Novel Pattern of Endoscopic Lung Cancer Resection.

BACKGROUND: Since the development of the uniportal video-assisted thoracoscopic surgery (VATS) technique, the use of uniportal VATS has become increasingly popular for the surgical resection of non-small cell lung cancer (NSCLC). The objective of this study is to introduce a novel modularly designed surgical pattern for uniportal VATS for lung cancer resection and to investigate the safety, feasibility, and efficacy of this novel method. MATERIALS AND METHODS: The clinical data of NSCLC patients who underwent a curative uniportal VATS lobectomy between March 2015 and April 2016, including via the modular pattern (MP) and the conventional pattern (CP), were retrospectively collected and analyzed. Perioperative and postoperative parameters, including the operation duration, estimated intraoperative blood loss, rate of conversion to thoracotomy, lymph node dissection number, and postoperative complications, were compared between the two groups. RESULTS: A total of 321 patients were identified, among whom 221 underwent MP uniportal VATS lobectomy and 100 were treated via CP uniportal VATS lobectomy. Patients in the MP group experienced a shorter operation duration (135.58 ± 47.16 minutes versus 148.86 ± 42.53 minutes, P = .017) and less estimated intraoperative blood loss (75.20 ± 37.99 mL versus 89.50 ± 41.11 mL, P = .003) than patients in the CP group. No significant difference was observed in the intraoperative conversion rate (2.7% versus 5.0%, P = .477), total number of lymph nodes dissected (24.67 ± 7.73 versus 25.34 ± 7.62, P = .471), postoperative drainage duration (4.86 ± 1.96 days versus 4.78 ± 2.10 days, P = .755), length of stay (9.60 ± 2.93 days versus 9.97 ± 2.80 days, P = .286), or incidence of postoperative complications between the two groups. No postoperative deaths occurred. CONCLUSIONS: MP uniportal VATS lobectomy combined with mediastinal lymphadenectomy appears to be a safe and feasible technique for the treatment of NSCLC. The use of this technique can reduce the operation duration and intraoperative blood loss.

Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma.

This corrects the article DOI: 10.1038/cddis.2016.260.