The aim of this study was to analyse and compare the chest radiographic and CT findings in patients with primary and secondary Sjögren's syndrome. We retrospectively evaluated the frequency of abnormality and findings of both the chest radiography (n=107) and CT (n=59) in patients with Sjögren's syndrome. Abnormal cases were classified into five patterns based on predominant CT findings. Chest radiographic and CT abnormalities were seen in 24 (22%) and in 34 (58%) patients, respectively. Most frequently observed abnormal findings were linear and reticular opacities on chest radiograph, and ground-glass opacity, interlobular septal thickening and intralobular interstitial thickening on CT in both primary and secondary Sjögren's syndrome. Centrilobular abnormalities were significantly more common in patients with primary Sjögren's syndrome (p=0.018). According to our CT classification, interstitial pneumonia (IP) pattern was the most common in patients with both primary and secondary Sjögren's syndrome. Bronchiolitis pattern was more common in patients with primary Sjögren's syndrome and lymphoproliferative disorder (LPD) pattern was only observed in primary Sjögren's syndrome. In conclusion, although the most frequently observed pattern in our CT classification was IP pattern in both primary and secondary Sjögren's syndrome, centrilobular abnormalities and LPD pattern were relatively characteristic in patients with primary Sjögren's syndrome.

Breast cancers can be divided into several types. Because triple-negative breast cancer (TNBC) is the most refractory to current anti-cancer therapies, efficient treatment has been urgently required. Members of the Bcl-2 family play pro- and anti-apoptotic roles in mitochondria-mediated apoptosis. Some Bcl-2 family members are expressed in breast cancer and influence the response to anti-cancer therapies. In this study, we investigated whether Bcl-2 inhibition could sensitize TNBC cells to the genotoxic drug doxorubicin (DR). Treatment with a combination of the Bcl-2 inhibitor ABT-199 and DR synergistically decreased the viability of the TNBC cell lines MDA-MB-231 and BT-549. In an apoptosis assay, the combination treatment resulted in only a marginal effect in BT-549 cells, whereas drastic apoptosis was induced in MDA-MB-231 cells treated with both ABT-199 and DR. Both caspase-8 and -9 were involved in the combination treatment-induced apoptosis. Short interfering RNA-mediated knockdown of Bcl-2 increased the sensitivity of both cell lines to DR. The combination treatment also significantly decreased the colony-forming ability of the TNBC cell lines. In a xenograft mouse model, oral administration of ABT-199 augmented the DR-induced antitumor effect on subcutaneously established MDA-MB-231 cells. These results indicate that the combination of DR with Bcl-2 inhibitors, including ABT-199, may be a promising treatment modality for TNBC patients.

Background: Anti PD-1/PD-L1 antibody therapy is a standard treatment for advanced non-small cell lung cancer (NSCLC), and PD-L1 immunohistochemistry is used as a predictive biomarker for therapeutic response. However, because not all NSCLC patients with a high PD-L1 respond, and some patients with low PD-L1 expression show durable benefit, more accurate, predictive biomarkers are needed. Circulating miRNA and miRNA packaged in extracellular vesicles (EVs) are considered to play a role in intercellular communication among immune cells and between immune cells and tumor cells and may represent a good source of mechanism-related biomarkers.

Senescence is a state of growth arrest induced not only in normal cells but also in cancer cells by aging or stress, which triggers DNA damage. Despite growth suppression, senescent cancer cells promote tumor formation and recurrence by producing cytokines and growth factors; this state is designated as the senescence‐associated secretory phenotype. In this study, we examined the susceptibility of senescent human breast cancer cells to immune cell‐mediated cytotoxicity. Doxorubicin (DXR) treatment induced senescence in 2 human breast cancer cell lines, MDA‐MB‐231 and BT‐549, with the induction of γH2AX expression and increased expression of p21 or p16. Treatment with DXR also induced the expression of senescence‐associated β‐galactosidase and promoted the production of pro‐inflammatory cytokines. Importantly, DXR‐treated senescent MDA‐MB‐231 cells showed increased sensitivity to 2 types of immune cell‐mediated cytotoxicity: cytotoxicity of activated CD4+ T cells and Ab‐dependent cellular cytotoxicity by natural killer cells. This increased sensitivity to cytotoxicity was partially dependent on tumor necrosis factor‐related apoptosis‐inducing ligand and perforin, respectively. This increased sensitivity was not observed following treatment with the senescence‐inducing cyclin‐dependent kinase‐4/6 inhibitor, abemaciclib. In addition, treatment with DXR, but not abemaciclib, decreased the expression of antiapoptotic proteins in cancer cells. These results indicated that DXR and abemaciclib induced senescence in breast cancer cells, but that they differed in their sensitivity to immune cell‐mediated cytotoxicity. These findings could provide an indication for combining anticancer immunotherapy with chemotherapeutic drugs or molecular targeting drugs.

Conventional PD‐L1 immunohistochemical tissue biopsies only predict 20%–40% of non‐small cell lung cancer (NSCLC) patients that will respond positively to anti‐PD‐1/PD‐L1 immunotherapy. Herein, we present an immunogold biochip to quantify single extracellular vesicular RNA and protein ( Au SERP) as a non‐invasive alternative. With only 20 μl of purified serum, PD‐1/PD‐L1 proteins on the surface of extracellular vesicles (EVs) and EV PD‐1/PD‐L1 messenger RNA (mRNA) cargo were detected at a single‐vesicle resolution and exceeded the sensitivities of their bulk‐analysis conventional counterparts, ELISA and qRT‐PCR, by 1000 times. By testing a cohort of 27 non‐responding and 27 responding NSCLC patients, Au SERP indicated that the single‐EV mRNA biomarkers surpass the single‐EV protein biomarkers in predicting patient responses to immunotherapy. Dual single‐EV PD‐1/PD‐L1 mRNA detection differentiated responders from non‐responders with an accuracy of 72.2% and achieved an NSCLC diagnosis accuracy of 93.2%, suggesting the potential for Au SERP to provide enhanced immunotherapy predictions and cancer diagnoses within the clinical setting.