Anomalous Cooper pair interference on Bi2Te3 surface

It is believed that the edges of a chiral p-wave superconductor host Majorana modes, relating to a mysterious type of fermions predicted seven decades ago. Much attention has been paid to search for p-wave superconductivity in solid-state systems, including recently those with strong spin-orbit coupling (SOC). However, smoking-gun experiments are still awaited. In this work, we have performed phase-sensitive measurements on particularly designed superconducting quantum interference devices constructing on the surface of topological insulators Bi2Te3, in such a way that a substantial portion of the interference loop is built on the proximity-effect-induced superconducting surface. Two types of Cooper interference patterns have been recognized at low temperatures. One is s-wave like and is contributed by a zero-phase loop inhabited in the bulk of Bi2Te3. The other, being identified to relate to the surface states, is anomalous for that there is a phase shift between the positive and negative bias current directions. The results support that the Cooper pairs on the surface of Bi2Te3 have a 2\pi Berry phase which makes the superconductivity p_x+ip_y-wave-like. Mesoscopic hybrid rings as constructed in this experiment are presumably arbitrary-phase loops good for studying topological quantum phenomena.Comment: supplementary material adde

Proximity effect at superconducting Sn-Bi2Se3 interface

We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions down to 250 mK and in different magnetic fields. A number of conductance anomalies were observed below the superconducting transition temperature of Sn, including a small gap different from that of Sn, and a zero-bias conductance peak growing up at lower temperatures. We discussed the possible origins of the smaller gap and the zero-bias conductance peak. These phenomena support that a proximity-effect-induced chiral superconducting phase is formed at the interface between the superconducting Sn and the strong spin-orbit coupling material Bi2Se3.Comment: 7 pages, 8 figure

Concomitant mutation status of ALK-rearranged non-small cell lung cancers and its prognostic impact on patients treated with crizotinib

Background: In non-small cell lung cancer (NSCLC), anaplastic lymphoma kinase (ALK) rearrangement characterizes a subgroup of patients who show sensitivity to ALK tyrosine kinase inhibitors (TKIs). However, the prognoses of these patients are heterogeneous. A better understanding of the genomic alterations occurring in these tumors could explain the prognostic heterogeneity observed in these patients. Methods: We retrospectively analyzed 96 patients with NSCLC with ALK detected by immunohistochemical staining (VENTANA anti-ALK(D5F3) Rabbit Monoclonal Primary Antibody). Cancer tissues were subjected to next-generation sequencing using a panel of 520 cancer-related genes. The genomic landscape, distribution of ALK fusion variants, and clinicopathological characteristics of the patients were evaluated. The correlations of genomic alterations with clinical outcomes were also assessed. Results: Among the 96 patients with immunohistochemically identified ALK fusions, 80 (83%) were confirmed by next-generation sequencing. TP53 mutation was the most commonly co-occurring mutation with ALK rearrangement. Concomitant driver mutations [2 Kirsten rat sarcoma viral oncogene homolog (KRAS) G12, 1 epidermal growth factor receptor (EGFR) 19del, and 1 MET exon 14 skipping] were also observed in 4 adenocarcinomas. Echinoderm microtubule associated protein-like 4 (EML4)-ALK fusions were identified in 95% of ALK-rearranged patients, with 16.2% of them also harboring additional non-EML4- ALK fusions. Nineteen non-EML4 translocation partners were also discovered, including 10 novel ones. Survival analyses revealed that patients concurrently harboring PIK3R2 alterations showed a trend toward shorter progression-free survival (6 vs. 13 months, P=0.064) and significantly shorter overall survival (11 vs. 32 months, P=0.004) than did PIK3R2-wild-type patients. Patients with concomitant alterations in PI3K the signaling pathway also had a shorter median overall survival than those without such alterations (23 vs. 32 months, P=0.014), whereas progression-free survival did not differ significantly. Conclusions: The spectrum of ALK-fusion variants and the landscape of concomitant genomic alterations were delineated in 96 NSCLC patients. Our study also demonstrated the prognostic value of concomitant alterations in crizotinib-treated patients, which could facilitate improved stratification of ALK-rearranged NSCLC patients in the selection of candidates who could optimally benefit from therapy

Beclin-1 Expression is a Predictor of Clinical Outcome in Patients with Esophageal Squamous Cell Carcinoma and Correlated to Hypoxia-Inducible Factor (HIF)-1α Expression

In the present study, we examined the relationship between Beclin-1 expression and HIF-1α expression in esophageal squamous cell carcinoma(ESCC). There was a loss of Beclin-1 protein expression in 33% of ESCCs. Beclin-1 expression significantly correlated with depth of invasion, lymph node metastasis and clinical stage. Among the 54 patients, The survival rate of the Beclin-1-positive group was better than that of the Beclin-1-negative group. Twenty-five of the 54 (46%) tumor specimens showed high levels of HIF-1α immunoreactivity. Beclin-1 expression was associated with HIF-1α expression. The survival rate of patients with Beclin-1-positive and HIF-1α-low tumors was significantly higher than that of the other groups. These results suggest that Beclin-1 and HIF-1α expression are important determinants of survival in ESCCs

DOK7 Inhibits Cell Proliferation, Migration, and Invasion of Breast Cancer via the PI3K/PTEN/AKT Pathway

Recently, increasing attention has been paid to the correlation between the expression of downstream of kinase 7 (DOK7) and the occurrence and development of various tumors. In this study, we clarified the effects of DOK7 in breast cancer. First, we showed that DOK7 expression was obviously reduced in the breast cancer tissues and lower levels of DOK7 linked to more aggressive behaviors and worse prognosis of patients. Furthermore, DOK7 expression of various breast cancer cell lines was lower than that of human noncancerous MCF-10A cells. Overexpression of DOK7 inhibited proliferation, migration, and invasion, while silencing DOK7 expression promoted the malignancy of breast cancer. In addition, overexpression of DOK7 suppressed tumor proliferation and lung metastasis in animal models. Finally, to investigate the possible signaling mechanism, we first found that the level of p-AKT protein was extremely downregulated and the level of PTEN protein was remarkably upregulated after overexpressing DOK7 in breast cancer cells. Repression of PTEN expression using PTEN siRNA or SF1670 (PTEN inhibitor) rescued the tumor-inhibiting effect induced by DOK7 overexpression, suggesting that DOK7 inhibits proliferation, migration, and invasion of breast cancer cells though the PI3K/PTEN/AKT pathway. These results suggest that the downregulation of DOK7 may become a novel breast cancer therapeutic target

Short-term response to immune-chemotherapy and immune features of a ceritinib-resistant patient with ROS1-rearranged lung adenocarcinoma

Patients with ROS1-rearranged non-small cell lung cancer (NSCLC) inevitably relapse after first-line targeted therapy with tyrosine kinase inhibitors. Efficacy of checkpoint inhibitor-based therapy on ROS1-positive NSCLC in second-line setting and change of immune factors during treatment are rarely studied. We report a ROS1-rearranged stage ⅢB lung adenocarcinoma patient who was resistant to ceritinib after developing a secondary ROS1 F2004L mutation. He received eight cycles of nivolumab plus chemotherapy and had an initial partial response, but brain metastases appeared in the seventh cycle. Lorlatinib was confirmed to have activity against CD74–ROS1 with F2004L in vitro, and was administered to this patient as the third-line therapy. The patient responded well to lorlatinib and had no relapse. We explored the tumor immune microenvironment (TIME) during immune-chemotherapy by multiplex immunohistochemistry, RNA sequencing, and multiplex plasma protein immunoassay. The results show that the TIME was active and plasma inflammatory factors were increased when the patient responded to immune-chemotherapy, while the plasma inhibitory checkpoint proteins, lymphocyte-activation gene 3, B and T lymphocyte attenuator, programmed cell death ligand 1 (PD-L1), and PD-1, were increased when the disease progressed. Moreover, the PD-L1 expression on tumor tissue was upregulated during treatment, predicting the limited benefit from immune-chemotherapy. This case report suggests that lorlatinib is a better choice than immune-chemotherapy in second-line setting for patients with similar genomic characteristics, and that monitoring the immune components during immunotherapy may help to predict disease response