In the ever-evolving landscape of cancer therapy, while cancer treatments such as chemotherapy, radiotherapy, and targeted therapy aim to eradicate malignant cells, they also inadvertently trigger cellular senescence in both cancerous and microenvironmental tissues. Therapy-induced senescence (TIS) can act as a barrier against tumor growth by halting cell proliferation in the short term, but the long-term persistence of therapy-induced senescent (TISnt) cells may pose a significant challenge in cancer management. Their distinct characteristics, like senescence-associated secretory phenotype (SASP), metabolic dysregulation, and immune evasion, make them exhibit remarkable heterogeneity to orchestrate the tumor microenvironment (TME), resulting in therapy resistance. However, how these TISnt cells functioning differently in cancer progression, and the intricate mechanisms by which they remodel the senescence-associated immunosuppressive microenvironment present challenges for improving anticancer therapy. Therefore, this review summarizes the heterogeneous TISnt cell phenotypes contributing to an accumulated senescent state, outlines their multidimensional interactions in the senescent microenvironment, and discusses current senescence-targeting strategies. Building on the current understanding of TIS, we propose potential avenues for improving TIS-targeting methodologies in the context of head and neck cancer, a representative heterogeneous malignancy, which can substantially enhance the efficacy of the "one-two punch" sequential treatment approach for head and neck cancer.
Humans ; Cellular Senescence/drug effects* ; Tumor Microenvironment ; Neoplasms/pathology* ; Senescence-Associated Secretory Phenotype

Objective:To design a morning quality assurance method for pencil-beam scanning proton system to achieve integrated measurement of multiple parameters.Methods:A functionally partitioned morning check phantom was designed and manufactured, which was fixed to a specific position on the treatment bed with a 3D-printed clip, along with the two-dimensional matrix ionization chamber, for consistency checks of proton field and beam-related parameters. Additionally, a groove for an imaging phantom was reserved on one side of the clip for the functional check of the onboard imaging guidance system. The sensitivity and specificity of the aforementioned morning check method were tested, demonstrating its effectiveness. The morning check data from a rotating beam treatment room at the Hefei Ion Medical Center over a continuous period of 7 months (126 d) were analyzed. The output, field flatness, symmetry, field size and the duration of morning check were observed.Results:The results showed that the changes in the output, field flatness, and symmetry were all within 1%, the change in the field size was within 0.5 mm, and the range variations for both 155 MeV and 240 MeV energy levels were within 1 mm. The changes in the spot size for the four energy levels of 100 MeV, 130 MeV, 160 MeV, and 190 MeV were all within 2%, and the spot position deviations were within 1.5 mm. The entire morning check process could be completed within 20 min.Conclusions:The morning check method designed and manufactured in this study specifically for pencil-beam scanning proton therapy can efficiently and integrally measure various proton system parameters and can be used as an implementation method for clinical proton therapy morning check.

Objective:To design a morning quality assurance method for pencil-beam scanning proton system to achieve integrated measurement of multiple parameters.Methods:A functionally partitioned morning check phantom was designed and manufactured, which was fixed to a specific position on the treatment bed with a 3D-printed clip, along with the two-dimensional matrix ionization chamber, for consistency checks of proton field and beam-related parameters. Additionally, a groove for an imaging phantom was reserved on one side of the clip for the functional check of the onboard imaging guidance system. The sensitivity and specificity of the aforementioned morning check method were tested, demonstrating its effectiveness. The morning check data from a rotating beam treatment room at the Hefei Ion Medical Center over a continuous period of 7 months (126 d) were analyzed. The output, field flatness, symmetry, field size and the duration of morning check were observed.Results:The results showed that the changes in the output, field flatness, and symmetry were all within 1%, the change in the field size was within 0.5 mm, and the range variations for both 155 MeV and 240 MeV energy levels were within 1 mm. The changes in the spot size for the four energy levels of 100 MeV, 130 MeV, 160 MeV, and 190 MeV were all within 2%, and the spot position deviations were within 1.5 mm. The entire morning check process could be completed within 20 min.Conclusions:The morning check method designed and manufactured in this study specifically for pencil-beam scanning proton therapy can efficiently and integrally measure various proton system parameters and can be used as an implementation method for clinical proton therapy morning check.

Objective:To explore the features the gait of elderly persons with type 2 diabetes and peri-pheral neuropathy.Methods:Twenty patients no less than 60 years old with type 2 diabetes and peripheral neuropathy (DPN) formed a DPN group, while 20 counterparts with type 2 diabetes but without peripheral neuropathy composed the DM group, and another 20 healthy counterparts served as a control group. The three groups were tested using the Swedish Qualisys motion capture system and their walking speed, step length, step width, stride frequency and stride length, bipedal foot support phase time, single foot support phase time, peak plantar pressure, and regional-holding time were collected and compared.Results:The average walking speed, stride length and stepping frequency of the DPN group were all significantly lower than the other 2 groups′ averages. Their bipedal support phase was significantly longer, but their single foot support phase time was significantly shorter. And in the DPN group the average first and second peak plantar pressures and the second peak pressure time were significantly greater than the other groups′ averages.Conclusions:Elderly patients with type 2 diabetes and peripheral neuropathy have significant gait abnormalities, decreased walking stability, as well as increased plantar pressure and plantar compression time.

Objective: To investigate the effect of miR-135a on the malignant biological behaviors of human laryngeal carcinoma epithelial Hep-2 cells and its sensitivity to oxaliplatin. Methods: Samples of laryngeal carcinoma tissues and para-cancerous tissues were collected from 10 patients who underwent laryngectomy in Nanyang Hospital Affiliated to Zhengzhou University-Nanyang City Center Hospital from January 2018 to June 2018. The expression of miR-135a in laryngeal carcinoma tissues and Hep-2 cells was detected by qPCR.After being transfected with miR-135 inhibitor, cell proliferation viability of Hep-2 cells was measured by CCK-8 assay, cell colony formation ability was detected by colony formation assay, and cell proliferation invasion and migration abilities were detected by Transwell analysis, and the expression of SOX2 protein in Hep-2 cells was detected by WB. Hep-2 cells transfected with miR-135 inhibitor were further treated with various concentrations (0.5, 1.0, 1.5 and 2.0 μmol/L) of oxaliplatin, and the cell proliferation viability was detected by CCK-8 while cell apoptosis was detected by Annexin-V-FITC/PI double staining flow cytometry. miR-135a inhibitor plasmid, control pcDNA empty vector (SOX2-Con) plasmid, and pcDNA-SOX2 (SOX2-OE) plasmid were transfected into Hep-2 cells to construct the miR-135a inhibitor+SOX2-Con group and miR-135a inhibitor+SOX2-OE group, and the cell viability, cell colony formation ability, cell invasion and migration ability in two groups were detected. Results: Compared with para-cancerous tissues, miR135a expression in laryngeal cancer tissues was significantly increased (P<0.01). Compared with normal NHP cells, miR-135a expression in Hep-2 cells was significantly increased (P<0.01). miR-135a inhibitor significantly reduced the expression level of miR-135a in Hep-2 cells (P<0.01). miR-135a knockdown significantly reduced the cell proliferation viability, cell colony number, migration, invasion and SOX2 expression in Hep-2 cells (all P <0.01), but significantly enhanced the sensitivity of Hep-2 cells to oxaliplatin (P<0.01). Compared with miR-135a inhibitor+SOX2-Con group, the cell proliferation viability, cell colony number, migration and invasion of Hep-2 cells in miR-135a inhibitor+SOX2-OE group were significantly increased (P<0.01); Meanwhile, the cells of the 2 groups were treated with different concentrations of oxaliplatin, and the results of CCK-8 assay showed that, compared with the miR-135a inhibitor+ SOX2-Con group, the cell proliferation viability of Hep-2 cells in miR-135a inhibitor+SOX2-OE group was significantly increased (P< 0.01). Conclusion: miR-135a knockdown inhibits the malignant biological behaviors and promotes oxaliplatin-sensitivity of Hep-2 cells possibly by inhibiting the expression of the transcription factor SOX2.