Activity

The prolactin inducible protein (PIP) is expressed to varying degrees in more than 90% of breast cancers (BCs). Although high levels of PIP expression in BC has been shown to correlate with better prognosis and patient response to chemotherapy, some studies suggest that PIP may also play a role in metastasis. Here, we investigated the role of PIP in BC using the well-established 4T1 and E0771 mouse BC cell lines. Stable expression of PIP in both cell lines did not significantly alter their proliferation, migration, and response to anticancer drugs in vitro compared to empty vector control. To assess the effect of PIP expression on breast tumorigenesis in vivo, the 4T1 syngeneic transplantable mouse model was utilized. In immunocompetent syngeneic BALB/c mice, PIP-expressing 4T1 primary tumors displayed delayed tumor onset and reduced tumor growth, and this was associated with higher percentages of natural killer cells and reduced percentages of type 2 T-helper cells in the tumor environment. The delayed tumor onset and growth were abrogated in immunodeficient mice, suggesting that PIP-mediated modulation of primary tumor growth involves an intact immune system. Paradoxically, we also observed that PIP expression was associated with a higher number of 4T1 colonies in the lungs in both the immunocompetent and immunodeficient mice. Gene expression analysis of PIP-expressing 4T1 cells (4T1-PIP) revealed that genes associated with tumor metastasis such as CCL7, MMP3 and MMP13, were significantly upregulated in 4T1-PIP cells when compared to the empty vector control (4T1-EV) cells. Collectively, these studies strongly suggest that PIP may possess a double-edge sword effect in BC, enhancing both antitumor immunity as well as metastasis.B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a blood cancer that originates from the abnormal proliferation of B-lymphoid progenitors. Cell population components and cell-cell interaction in the bone marrow microenvironment are significant factors for progression, relapse, and therapy resistance of BCP-ALL. In this study, we identified specifically expressed genes in B cells and myeloid cells by analyzing single-cell RNA sequencing data for seven BCP-ALL samples and four healthy samples obtained from a public database. Integrating 1356 bulk RNA sequencing samples from a public database and our previous study, we found a total of 57 significant ligand-receptor pairs (24 upregulated and 33 downregulated) in the autocrine crosstalk network of B cells. Via assessment of the communication between B cells and myeloid cells, another 29 ligand-receptor pairs were discovered, some of which notably affected survival outcomes. A score-based model was constructed with least absolute shrinkage and selection operator (LASSO) using these ligand-receptor pairs. Patients with higher scores had poorer prognoses. This model can be applied to create predictions for both pediatric and adult BCP-ALL patients.

Breast cancer is the most common women malignancy worldwide, while estrogen receptor alpha positive type accounts for two third of all breast cancers. Although ER alpha positive breast cancer could be effectively controlled by endocrine therapy, more than half of the cases could develop endocrine resistance, making it an important clinical issue in breast cancer treatment. Thus, decoding the detailed mechanism, which controls ER alpha signaling activation and ER alpha protein stability, is of great importance for the improvement of breast cancer therapy. Several zinc finger proteins were shown to mediate the ubiquitination process and modulate protein stability. Thus, we further explore the function of Zinc finger protein 213 on ER alpha protein stability and tamoxifen resistance.

CCK8 and Edu assay was used to measure cell proliferation. RNA sequence was performed by Ingenuity pathway analysis. The ER alpha signaling activities were measured with luciferase assay, real-time quantitative PCR,and western bast cancer. Targeting ZNF213 could be an appealing strategy for ER alpha positive breast cancer.Mutations of the proto-oncogene KRAS are the most frequent gain-of-function alterations found in cancer. KRAS is mutated in about 30% of all human tumors, but it could reach more than 90% in certain cancer types such as pancreatic adenocarcinoma. Although historically considered to be undruggable, a particular KRAS mutation, the G12C variant, has recently emerged as an actionable alteration especially in non-small cell lung cancer (NSCLC). KRASG12C and pan-KRAS inhibitors are being tested in clinical trials and have recently shown promising activity. CCS-1477 chemical structure Due to the difficulties in direct targeting of KRAS, other approaches are being explored. The inhibition of target upstream activators or downstream effectors of KRAS pathway has shown to be moderately effective given the evidence of emerging mechanisms of resistance. Various synthetic lethal partners of KRAS have recently being identified and the inhibition of some of those might prove to be successful in the future. The study of escape mechanisms to KRAS inhibition could support the utility of combination strategies in overcoming intrinsic and adaptive resistance and enhancing clinical benefit of KRASG12C inhibitors. Considering the role of the microenvironment in influencing tumor initiation and promotion, the immune tumor niche of KRAS mutant tumors has been deeply explored and characterized for its unique immunosuppressive skewing. However, a number of aspects remains to be fully understood, and modulating this tumor niche might revert the immunoresistance of KRAS mutant tumors. Synergistic associations of KRASG12C and immune checkpoint inhibitors are being tested.

Lung cancer screening using low-dose computed tomography (LDCT) often leads to unnecessary biopsy because of the low specificity among patients with pulmonary nodules ≤10 mm. Circulating genetically abnormal cells (CACs) can be used to discriminate lung cancer from benign lung disease. To examine the diagnostic value of CACs in detecting lung cancer for patients with malignant pulmonary nodules ≤10 mm.

In this prospective study, patients with pulmonary nodules ≤10 mm who were detected at four hospitals in China from January 2019 to January 2020 were included. CACs were detected using fluorescence

hybridization. All patients were confirmed as lung cancer or benign disease by further histopathological examination. Multivariable logistic regression models were established to detect the presence of lung cancer using CACs and other associated characteristics. Receiver operating characteristic analysis was used to evaluate the performance of CACs for lung cancer diagnosis.

Overall, 125 patients were included and analyzed.