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Int J Mol Sci ; 22(18)2021 Sep 11.
Article in English | MEDLINE | ID: covidwho-1470886


During the last decade, we have persistently addressed the question, "how can the innate immune system be used as a therapeutic tool to eliminate cancer?" A cancerous tumor harbors innate immune cells such as macrophages, which are held in the tumor-promoting M2 state by tumor-cell-released cytokines. We have discovered that these tumor-associated macrophages (TAM) are repolarized into the nitric oxide (NO)-generating tumoricidal M1 state by the dietary agent curcumin (CC), which also causes recruitment of activated natural killer (NK) cells and cytotoxic T (Tc) cells into the tumor, thereby eliminating cancer cells as well as cancer stem cells. Indications are that this process may be NO-dependent. Intriguingly, the maximum blood concentration of CC in mice never exceeds nanomolar levels. Thus, our results submit that even low, transient levels of curcumin in vivo are enough to cause repolarization of the TAM and recruitment NK cells as well as Tc cells to eliminate the tumor. We have observed this phenomenon in two cancer models, glioblastoma and cervical cancer. Therefore, this approach may yield a general strategy to fight cancer. Our mechanistic studies have so far implicated induction of STAT-1 in this M2→M1 switch, but further studies are needed to understand the involvement of other factors such as the lipid metabolites resolvins in the CC-evoked anticancer pathways.

Curcumin/therapeutic use , Glioblastoma/drug therapy , Neoplasms, Experimental/drug therapy , Uterine Cervical Neoplasms/drug therapy , Animals , Female , Glioblastoma/immunology , Glioblastoma/pathology , Humans , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Mice , Neoplasms, Experimental/immunology , Neoplasms, Experimental/pathology , Nitric Oxide/immunology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/pathology , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/pathology , Uterine Cervical Neoplasms/immunology , Uterine Cervical Neoplasms/pathology
Obstet Gynecol ; 135(5): 1070-1083, 2020 05.
Article in English | MEDLINE | ID: covidwho-1455363


OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of adjuvant human papillomavirus (HPV) vaccination in preventing recurrent cervical intraepithelial neoplasia (CIN) 2 or greater after surgical excision. DATA SOURCES: Electronic databases (Cochrane, PubMed, EMBASE, MEDLINE, Scopus, and were searched for studies comparing surgical excision alone to surgical excision with adjuvant HPV vaccination for CIN 2 or greater. Studies published from January 1990 to January 2019 were included. METHODS: A total of 5,901 studies were reviewed. The primary outcomes evaluated included: recurrence of CIN 2 or greater, CIN 1 or greater, and HPV 16,18 associated CIN within 6-48 months. We used Covidence software to assist with screening, and meta-analysis was performed using Review Manager. TABULATION, INTEGRATION, AND RESULTS: Six studies met inclusion criteria and were included in the final analysis. In total 2,984 women were included; 1,360 (45.6%) received adjuvant HPV vaccination after surgical excision, and 1,624 (54.4%) received either placebo or surgical management alone for CIN 2 or greater. Recurrence of CIN 2 or greater occurred within 6-48 months in 115 women (3.9%) overall; however, recurrence was significantly lower for vaccinated women: 26 of 1,360 women (1.9%) vs 89 of 1,624 unvaccinated women (5.9%) (relative risk [RR] 0.36 95% CI 0.23-0.55). The risk of CIN 1 or greater was also significantly lower with adjuvant HPV vaccination, occurring in 86 of 1,360 vaccinated women (6.3%) vs 157 of 1,624 unvaccinated women (9.7%) (RR 0.67 95% CI 0.52-0.85). Thirty-five women developed recurrent CIN 2 or greater lesions specific to HPV 16,18; nine received adjuvant vaccination (0.9%) vs 26 who were unvaccinated (2.0%) (RR 0.41 95% CI 0.20-0.85). CONCLUSION: Adjuvant HPV vaccination in the setting of surgical excision for CIN 2 or greater is associated with a reduced risk of recurrent cervical dysplasia overall and a reduction in the risk of recurrent lesions caused by the most oncogenic strains (HPV 16,18). Human papillomavirus vaccination should therefore be considered for adjuvant treatment in patients undergoing surgical excision for CIN 2 or greater. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019123786.

Cervical Intraepithelial Neoplasia/drug therapy , Neoplasm Recurrence, Local/prevention & control , Papillomavirus Infections/complications , Papillomavirus Vaccines/therapeutic use , Uterine Cervical Neoplasms/drug therapy , Adult , Cervical Intraepithelial Neoplasia/surgery , Cervical Intraepithelial Neoplasia/virology , Chemotherapy, Adjuvant , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/virology , Papillomavirus Infections/virology , Treatment Outcome , Uterine Cervical Neoplasms/surgery , Uterine Cervical Neoplasms/virology , Young Adult