BackgroundCancer has become increasingly prevalent in China over the past few decades. Among the factors that determine the quality of life of cancer patients, pain has commonly been recognized as a most critical one; it could also lead to the ineffective treatment of the cancer. Driven by the need for better pain management for cancer patients, our research team developed a mobile-based Intelligent Pain Management System (IPMS).ObjectiveOur objective was to design, develop, and test the IPMS to facilitate real-time pain recording and timely intervention among cancer patients with pain. The system’s usability, feasibility, compliance, and satisfaction were also assessed.MethodsA sample of 46 patients with cancer pain symptoms were recruited at the Oncology Center of Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Chongming Branch (hereinafter referred to as “the Oncology Center”). In a pretest, participants completed a pain management knowledge questionnaire and were evaluated using the baseline cancer pain assessment and Karnofsky Performance Status (KPS) evaluation. The participants were then randomly assigned into two groups (the trial group and the control group). After a 14-day trial period, another round of cancer pain assessment, KPS evaluation and pain management knowledge assessment were repeated. In the trial group, the data were fully automatically collected by the IPMS. In the control group, the data were collected using conventional methods, such as phone interviews or door-to-door visits by physicians. The participants were also asked to complete a satisfaction questionnaire on the use of the IPMS.ResultsAll participants successfully completed the trial. First, the feasibility of IPMS by observing the number of daily pain assessments recorded among patients was assessed. Second, the users’ satisfaction, effectiveness of pain management, and changes in the quality of their lives were evaluated. All the participants gave high satisfaction score after they used IMPS. Both groups reported similar pain scores and KPS scores at the baseline. At the end of the trial, the mean pain score of the trial group was significantly lower than of the control group (P<.001). The ending KPS score of the trial group was significantly higher than of the control group (P<.001). The improvement of pain management knowledge score in the trial group was more pronounced than that in the control group (P<.001).ConclusionsThis study provided preliminary data to support the potentials of using IPMS in cancer pain communication between patients and doctors and to provide real-time supportive intervention on a convenient basis at a low cost. Overall, the IPMS can serve as a reliable and effective approach to control cancer pain and improve quality of life for patients with cancer pain.Trial RegistrationClinicaltrials.gov NCT02765269; http://clinicaltrials.gov/ct2/show/NCT02765269 (Archived by WebCite at http://www.webcitation.org/6rnwsgDgv)

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BackgroundOvarian clear cell carcinoma (OCCC) arises from endometriosis and represents a difficult-to-treat gynaecological malignancy, in part, because its spatial intratumour heterogeneity and temporal evolutionary trajectories have not been explicitly defined.MethodsWe performed whole-genome sequencing on six pathologically confirmed patients with OCCC. An R package named KataegisPortal was developed to identify and annotate loci of localised hypermutations. Immunohistochemical staining was conducted on a tissue microarray containing 143 OCCC specimens.ResultsMultiregion analysis demonstrated considerable degrees of subclonal diversification, ascribable to dynamic mutagenic processes, as well as macroevolutionary events including the acquisition of aneuploidy and chromoplexy. KataegisPortal unveiled APOBEC-mediated kataegis in the early phases of OCCC pathogenesis. We further showed evidence that APOBEC3A and APOBEC3B were frequently expressed in OCCC and possibly regulated by the MAPK pathway. Notably, APOBEC3B-expressing OCCC displayed favourable prognosis and appreciable immunogenicity manifested by marked cytotoxic T-cell infiltration.ConclusionsThese results point to an appealing model of punctuated tumour evolution underlying OCCC neoplastic transformation and progression, which may pose formidable challenges of early detection and intervention, and indicate the intratumour heterogeneity of cancer-driving alterations, yielding important implications for molecular diagnosis and targeted treatment of this lethal disease.

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GSDME is a newly recognized executor of cellular pyroptosis, and has been recently implicated in tumor growth and immunity. However, knowledge about the molecular regulators underlying GSDME abundance remains limited. Here, we performed integrative bioinformatics analyses and identified that epithelial-mesenchymal transition (EMT) gene signatures exhibited positive correlation with GSDME levels across human cancers. A causal role was supported by the observation that EMT dictated GSDME reversible upregulation in multiple experimental models. Mechanistically, transcriptional activation of GSDME was directly driven by core EMT-activating transcription factors ZEB1/2, which bound to the GSDME promoter region. Of functional importance, elevated GSDME in mesenchymally transdifferentiated derivatives underwent proteolytic cleavage upon antineoplastic drug exposure, leading to pyroptotic cell death and consequent cytokine release. Taken together, our findings pinpointed a key transcriptional machinery controlling GSDME expression and indicated potential therapeutic avenues to exploit GSDME-mediated inflammatory pyroptosis for the treatment of mesenchymal malignancies.

Background In a previous study, persistent pain was suggested to be a risk factor for tumor patients. However, the mechanism underlying this phenomenon is still unclear. Substance P (SP), a pain-related neuropeptide secreted by the neural system and the immune system, plays an important role in the induction and maintenance of persistent pain. Methods In this study, in order to explore whether SP participates in the influence of pain on tumor progression, the serum samples of lung cancer and breast cancer patients were collected and tested. An elevated expression of SP was found in patients with pain. Results Cell pharmacological experiments revealed that SP can upregulate the expression of Toll-like receptor-4 (TLR-4) in tumor cells and increase the proliferation, migration, and invasive activity of tumor cells. As high expression of TLR-4 has the ability to enhance the biological activity of tumor cells, TLR-4 is thought to be involved in SP-induced tumor proliferation, migration, and invasion. Treatment of tumor cells with Aprepitant, a specific blocker of the NK-1 receptor, could reduce the expression of TLR-4 and reduce the proliferation, invasion, and migration activities of tumor cells; further proof of the influence of SP on TLR-4 expression depends on the NK-1 receptor located in tumor cells. Conclusions Based on the results above, we proposed a possible mechanism underlying pain affecting tumor progression: The presence of pain increases the content of SP in patients’ blood, and elevated SP increases the expression of tumor TLR-4 by acting on the NK-1 receptor, which ultimately affects the biological activity of the tumor.

Objective: This study was aimed to investigate the patient's characteristics and histopathologic findings of risk-reducing salpingo-oophorectomy (RRSO) conducted in Asan Medical Center. Methods: We retrospectively analyzed the medical records of germline BRCA1/BRCA2 mutation carriers who underwent RRSO at Asan Medical Center from January 2009 to December 2020. Results: A total of 274 patients underwent RRSO (136 BRCA1, 135 BRCA2, 3 BRCA1, and 2 mutation carriers). The mean age at the time of surgical intervention was similar for BRCA1 and BRCA2 mutation carriers (46.9 and 46.3, respectively). Only 6 surgeries were performed in 2009, while 48 were performed in 2020, with more and more over time. Eight out of 136 (5.8%) BRCA1 carriers and 9 out of 135 (6.7%) BRCA2 carriers were unaffected, and others were breast cancer patients. According to the pathologic reports, 6 out of 136 (4.4%) BRCA1 mutation group were diagnosed with occult malignancy such as tubal cancer, and 4 out of 137 (3.0%) were pre-malignant lesions, including serous tubal intraepithelial lesion (STIL) or serous tubal intraepithelial carcinoma (STIC). In the BRCA2 mutation group, only 1 out of 135 (0.7%) was diagnosed with STIC, and no occult cancer was found. Conclusion: According to our study, germline BRCA mutation carriers tend to go through RRSO in their mid to late 40s, and most of the patients were breast cancer patients. Occult tubal cancer or premalignant lesion (STIC, STIL) were diagnosed more frequently in BRCA1 carriers than BRCA2 carriers.

This case study reviews the design and development of a mobile-based intelligent pain management system (IPMS) app in cancer patient care and pain management in a rural hospital in China. Healthcare professionals were involved throughout the design to the evaluation stages. The IPMS facilitated real-time pain recording and timely intervention among cancer patients with pain. To evaluate the effectiveness of the IPMS, a clinical trial was administrated under the supervision of healthcare professionals. The result confirmed that the IPMS was a feasible, effective, and low-cost pain management tool for cancer patients and healthcare professionals. This case provides preliminary data to support the potentials of using IPMS in cancer pain management and emphasized that the involvement of healthcare professional throughout the system development lifecycle is crucial to the successful implementation of the IPMS.