Chemotherapy, including microtubule (MT)-interacting agents, can enhance the tumor-eradicating activity of replication-competent adenoviruses. The purpose of this study was to obtain more insight into the mechanism underlying this enhancement that may be exploited for the development of improved therapy. Two MT-interacting agents with opposite activity, paclitaxel (PTX) that stabilizes and vincristine (VCR) that destabilizes MTs, were found to synergistically enhance adenoviral oncolysis in non-small-cell lung cancer (NSCLC) cells. To explore the possibility that these drugs affect the viral life cycle by modulating adenoviral gene expression, we used a quantitative reverse transcription-polymerase chain reaction assay and found that PTX, but not VCR, increased the expression of E1A13S, ADP and Penton genes, which correlated with an increase in viral particle assembly and release. Next, the effect of combined treatment on cell-cycle progression was studied. Both drugs suppressed adenovirus-induced S-phase arrest and instead caused G2/M arrest, which was accompanied by an increase in apoptotic cells. Taken together, the enhancement of oncolysis by MT-interacting drugs appears not to require specific MT transport or scaffold functions. Our findings suggest that MT-interacting drug-induced cellular signals that modulate cell-cycle arrest and apoptosis are primarily on the basis of their oncolysis-enhancing activity.

Objectives: To identify the relevance of neuroendocrine differentiation in non-small cell lung cancer and its correlation with different pathological features. Materials and Methods: A total number of 30 cases of per cutaneous CT guided biopsies of primary non-small lung cancer were collected in the pathology department of Misr University for Science and Technology Giza, Egypt and private practice in the time period from January 2018 till December 2020. Immunohistochemical study for neuroendocrine differentiation was performed using mono clonal antibodies against synaptophysin, chromogranin A and CD56. For all selected cases, clinical and pathological data such as age, gender, histologic types, grade and clinical stage were collected, tabulated and statistically analyzed with the results of neuroendocrine markers expression. Cases with incomplete pathological data and cases with histologic picture of neuroendocrine differentiation were excluded. Results: A total number of 30 cases of primary non-small lung cancer were enrolled in this study. The median age of patients was 61.5 years. There were 21 (70%) males and 9 (30%) females. Regarding neuroendocrine markers, positivity for either marker was identified in 23.3% of non-small cell lung cancer. Chromogranin A was positively expressed in 9 (30%) of cases, synaptophysin was positively expressed in 7 (23.3%) of cases and CD56 was positively expressed in 5 (16.7%) of cases. Only 2 cases (6.7%) showed co-expression of two markers. It was found that there was a high significant relation between chromogranin A expression and clinical stage. Chromogranin A expression was significantly higher in stage III than stage I and II (P<0.001). There was no statistical significant difference between synaptophysin, chromogranin A and CD56 expressions and the rest of the studied pathologic data. Conclusion: A considerable number of non-small cell lung cancer has neuroendocrine differentiation for at least one neuroendocrine marker despite absence of morphologic features. Much less number of cases showed expression of two markers. A reasonable panel of neuroendocrine markers is recommended to detect this differentiation which may have a clinical impact and optimize an alternative therapeutic option.