Pancreatic cancer (PaCa) is an aggressive malignancy with a high mortality rate and a poor prognosis. To evaluate treatment outcomes of patients with pancreatic cancer over the past three decades, data from the Surveillance, Epidemiology, and End Results (SEER) registries were used to assess the survival of patients with PaCa. A total of 63,530 patients diagnosed with pancreatic cancer between 1981 and 2010 were identified from nine original SEER registries. The 1-year relative survival rates (RSRs) improved each decade, from 17.0% to 19.9% to 28.2% (p < 0.0001), with a larger increase during the third decade than during the second decade. However, the long-term survival rates have remained very low. The 5-year RSRs increased from 3.1% to 4.4% to 6.9% over these three decades--i.e., still only few patients with PaCa survive more than 5 years. Furthermore, our analysis demonstrated that the survival rates for all the patients with pancreatic cancer were lower in patients of lower socioeconomic status and black race. These results will help predict future trends in PaCa incidence and survival, contribute to better-designed clinical trials by eliminating disparities that may affect the results, and thereby improve the clinical management and outcomes of PaCa.

The striatin-interacting phosphatase and kinase (STRIPAK) complexes integrate extracellular stimuli that result in intracellular activities. Previously, we discovered that STRIPAK is a key machinery responsible for loss of the Hippo tumor suppressor signal in cancer. Here, we identified the Hippo-STRIPAK complex as an essential player in the control of DNA double-stranded break (DSB) repair and genomic stability. Specifically, we found that the mammalian STE20-like protein kinases 1 and 2 (MST1/2), independent of classical Hippo signaling, directly phosphorylated zinc finger MYND type–containing 8 (ZMYND8) and hence resulted in the suppression of DNA repair in the nucleus. In response to genotoxic stress, the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway was determined to relay nuclear DNA damage signals to the dynamic assembly of Hippo-STRIPAK via TANK-binding kinase 1–induced (TBK1-induced) structural stabilization of the suppressor of IKBKE 1– sarcolemma membrane–associated protein (SIKE1-SLMAP) arm. As such, we found that STRIPAK-mediated MST1/2 inactivation increased the DSB repair capacity of cancer cells and endowed these cells with resistance to radio- and chemotherapy and poly(ADP-ribose)polymerase (PARP) inhibition. Importantly, targeting the STRIPAK assembly with each of 3 distinct peptide inhibitors efficiently recovered the kinase activity of MST1/2 to suppress DNA repair and resensitize cancer cells to PARP inhibitors in both animal- and patient-derived tumor models. Overall, our findings not only uncover what we believe to be a previously unrecognized role for STRIPAK in modulating DSB repair but also provide translational implications of cotargeting STRIPAK and PARP for a new type of synthetic lethality anticancer therapy.

Background: High frequency of loss of heterozygosity (LOH) was found at D7S486 in primary gastric cancer (GC). And we found a high frequency of LOH region on 7q31 in primary GC from China, and identified D7S486 to be the most frequent LOH locus. This study was aimed to determine what genes were affected by the LOH and served as tumor suppressor genes (TSGs) in this region. Here, a high-throughput single nucleotide polymorphisms (SNPs) microarray fabricated in-house was used to analyze the LOH status around D7S486 on 7q31 in 75 patients with primary GC. Western blot, immunohistochemistry, and RT-PCR were used to assess the protein and mRNA expression of TESTIN (TES) in 50 and 140 primary GC samples, respectively. MTS assay was used to investigate the effect of TES overexpression on the proliferation of GC cell lines. Mutation and methylation analysis were performed to explore possible mechanisms of TES inactivation in GC.Results: LOH analysis discovered five candidate genes (ST7,FOXP2,MDFIC,TESandCAV1) whose frequencies of LOH were higher than 30%. However, onlyTESshowed the potential to be a TSG associated with GC. Among 140 pairs of GC samples, decreasedTESmRNA level was found in 96 (68.6%) tumor tissues when compared with matched non-tumor tissues (p< 0.001). Also, reduced TES protein level was detected in 36 (72.0%) of all 50 tumor tissues by Western blot (p= 0.001). In addition, immunohistochemical staining result was in agreement with that of RT-PCR and Western blot. Down regulation of TES was shown to be correlated with tumor differentiation (p= 0.035) and prognosis (p= 0.035, log-rank test). Its overexpression inhibited the growth of three GC cell lines. Hypermethylation ofTESpromoter was a frequent event in primary GC and GC cell lines. However, no specific gene mutation was observed in the coding region of theTESgene.Conclusions: Collectively, all results support the role ofTESas a TSG in gastric carcinogenesis and thatTESis inactivated primarily by LOH and CpG island methylation.

Background: There clearly is a need for effective chemotherapy for early-stage, high-risk patients with human cervical carcinoma. Vinblastine (VBL) is a key microtubule inhibitor, but unproven in its mechanisms as an important antitumor agent in cervical carcinoma.

Purpose Glioma is a rare and highly malignant tumor that affects the nervous system. While studies have been conducted on the occurrence and survival rates of glioma patients, there is currently a lack of comprehensive and large population research focusing on long-term trends in glioma incidence, survival rates, and associated risk factors. Methods Data for 30,209 patients with glioma was collected from the Surveillance, Epidemiology and End Results (SEER) database from eight registries between 1975 and 2014. By analyzing Kaplan-Meier curves, we assessed the survival differences between sex, race, and socioeconomic status (SES) over a 40-year period. Additionally, Cox regression analysis was employed to examine the impact of various risk factors, including age, race, income, grade, tumor site, surgery, tumor size, radiotherapy, chemotherapy and postoperative radiotherapy (PORT) with or without on glioma survival. Results Our study found that the incidence and number of glioma cases are on the rise. The incidence rates per decade from 1975 to 2014 were 2.6/100,000, 3.3/100,000, 4.0/100,000, 4.2/100,000, and 4443, 6441, 8893, and 10432, respectively. Besides, the 10-year relative survival rates (RSRs) for glioma were 23.19%, 30.80%, 34.67%, and 38.38%, respectively. In addition, the median survival per decade was 9, 10, and 9 months from 1975 to 2004, compared with 13 months from 2005 to 2014. Our findings revealed that advanced age, race, low household income, high-grade (poorly differentiated and undifferentiated), bilateral tumor occupying lesions, large tumor diameter, and failure to receive surgery/chemotherapy/radiation/PORT are risk factors for glioma. Conclusion The results of this study indicate a rising incidence of glioma cases. While there have been improvements in survival rates over time, it is crucial to acknowledge that long-term survival rates for glioma patients remain relatively low. Taken together, our study highlights the need for further in-depth research to improve treatment strategies.