Viral infections can reduce early cancer development through enhancement of cancer immunosurveillance. This study was performed to analyse this effect of viral infection in a mouse model of solid tumor.
Methods
The experimental model used was the effect of BALB/c mouse infection by lactate dehydrogenase-elevating virus on AB1 mesothelioma cancer development.
Results
Acute infection with lactate dehydrogenase-elevating virus strongly reduced in vivo early AB1 mesothelioma growth and death resulting from cancer development. This effect was not due to a direct cytolytic effect of the virus on AB1 cells, but to an in vivo activation of natural killer cells. Gamma-interferon production rather than cytotoxic activity against AB1 cells mediated this protective effect. This gamma-interferon production by natural killer cells was dependent on interleukin-12 production.
Conclusions
Together with other reported effects of infectious agents on cancer development, this observation may support the hypothesis that enhancement of innate immunosurveillance against tumors may result from infection with common infectious agents through modulation of the host immune microenvironment.
OBJECTIVE: To estimate the effect of the selective serotonin reuptake inhibitor sertraline on hot flush frequency and severity in perimenopausal and postmenopausal women. METHODS: We performed a randomized, blinded, placebo-controlled trial in women aged 40 to 60 years with 14 or more hot flushes per week (N=99). Women were randomly assigned initially to daily oral sertraline (50 mg) or identical placebo for 2 weeks. If no substantial side effects were noted, the dose was increased to two tablets daily (100 mg sertraline or placebo) and continued for an additional 4 weeks. Hot flush frequency and severity were recorded on a daily diary. Hot flush score was calculated as frequency multiplied by severity. Participants also completed questionnaires addressing quality of life, menopausal symptoms, sleep quality, sexual function, mood, and side effects. RESULTS: After 6 weeks of treatment, hot flush frequency decreased similarly in both the placebo (38%) and sertraline (39%) groups (P=.94). Mean hot flush scores also decreased similarly in both groups (41% and 42%, respectively, P=.86). Compared with placebo, women in the sertraline group were more likely to report gastrointestinal complaints, dry mouth, and dizziness. Treatment with sertraline also resulted in greater worsening of scores on the Medical Outcomes Study (MOS) Short Form 36 standardized physical component and the global Female Sexual Function Index. Results were similar in women at least 80% adherent to study medication. CONCLUSION: Treatment with sertraline did not improve hot flush frequency or severity in generally healthy perimenopausal and postmenopausal women, but was associated with bothersome side effects. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00283192 LEVEL OF EVIDENCE: I. 相似文献
In 2019, the FLOT4 protocol was established as the new standard for perioperative therapy in patients with locally advanced gastroesophageal and gastric cancer. Whether this protocol is beneficial in a real-world setting remains a question with limited answers to date. In our study, a large cohort of unselected patients treated with FLOT4 was analyzed and compared to protocols based on 5-FU/platinum derivative. This retrospective analysis included patients with locally advanced gastroesophageal and gastric cancer treated with perioperative FLOT or 5-FU/platinum derivative at University Hospital, Bonn between 2010 and 2022 in a curative setting (n = 99). Overall survival, disease-free survival, therapy response and therapy complications were analyzed. Patients treated with FLOT showed a statistically significant longer median overall survival of 57.8 vs 28.9 months (HR: 0.554, 95% CI: 0.317-0.969, P = .036). Moreover, pathological tumor regression (pTR) was significantly higher in the FLOT group compared to the 5-FU/platinum group (P = .001). Subgroup analysis showed a favorable survival benefit for the FLOT vs 5-FU/platinum derivate in patients with AEG and non-signet cell carcinoma. Overall, FLOT was tolerated well but CTCAE ≥3 grade neutropenia and diarrhea occurred more often within the FLOT group. Similar to the prospective phase II/III trials, FLOT4 was the best protocol for patients with locally advanced gastroesophageal and gastric cancer as perioperative therapy in terms of overall survival and pathological response rate compared to 5-FU/platinum derivative protocols. Interestingly, patients with gastroesophageal cancer benefitted more from this therapy. In contrast, patients with signet ring cells appear not to benefit from addition of docetaxel. 相似文献
Sexuality and Disability - Diabetes mellitus is a prevalent chronic worldwide disease, and sexual dysfunction is a common complication of this disease. Diabetes and its disabling complications... 相似文献
Osteoclasts, the multinucleated bone-resorbing cells, arise through fusion of precursors from the myeloid lineage. However,
not all osteoclasts are alike; osteoclasts at different bone sites appear to differ in numerous respects. We investigated
whether bone marrow cells obtained from jaw and long bone differed in their osteoclastogenic potential. Bone marrow cells
from murine mandible and tibiae were isolated and cultured for 4 and 6 days on plastic or 6 and 10 days on dentin. Osteoclastogenesis
was assessed by counting the number of TRAP+ multinucleated cells. Bone marrow cell composition was analyzed by FACS. The expression of osteoclast- and osteoclastogenesis-related
genes was studied by qPCR. TRAP activity and resorptive activity of osteoclasts were measured by absorbance and morphometric
analyses, respectively. At day 4 more osteoclasts were formed in long bone cultures than in jaw cultures. At day 6 the difference
in number was no longer observed. The jaw cultures, however, contained more large osteoclasts on plastic and on dentin. Long
bone marrow contained more osteoclast precursors, in particular the myeloid blasts, and qPCR revealed that the RANKL:OPG ratio
was higher in long bone cultures. TRAP expression was higher for the long bone cultures on dentin. Although jaw osteoclasts
were larger than long bone osteoclasts, no differences were found between their resorptive activities. In conclusion, bone
marrow cells from different skeletal locations (jaw and long bone) have different dynamics of osteoclastogenesis. We propose
that this is primarily due to differences in the cellular composition of the bone site-specific marrow. 相似文献