Systemic treatment options for non-small cell lung cancer after failure of previous immune checkpoint inhibitors: a bayesian network meta-analysis based on randomized controlled trials.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these patients. We designed a network meta-analysis (NMA) to evaluate systemic treatment options for NSCLC after failure of ICIs. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched, then literature screening was followed by NMA. We included all Phase II and III randomized controlled trials (RCTs). Progression-free survival (PFS) and overall survival (OS) used hazard ratio (HR) for evaluation. Objective response rate (ORR) and adverse events (AEs) used odds ratio (OR) and relative risk (RR) effect sizes, respectively. R software was applied to compare the Bayesian NMA results. RESULTS: We finally included 6 studies. 1322 patients received ICI plus Chemotherapy (ICI + Chemo), ICI plus Anti-angiogenic monoclonal antibody (ICI + Antiangio-Ab), ICI plus Tyrosine kinase inhibitor (ICI + TKI), Tyrosine kinase inhibitor plus Chemotherapy (TKI + Chemo), Standard of Care (SOC), Chemotherapy (Chemo). TKI + Chemo is associated with longer PFS, higher ORR (surface under cumulative ranking curve [SUCRA], 99.7%, 88.2%), ICI + TKI achieved the longest OS (SUCRA, 82.7%). ICI + Antiangio-Ab was granted the highest safety rating for adverse events (AEs) of any grade, AEs greater than or equal to grade 3 and AEs of any grade leading to discontinuation of treatment (SUCRA, 95%, 82%, 93%). CONCLUSIONS: For NSCLC after failure of ICIs, TKI + Chemo was associated with longer PFS and higher ORR, while ICI + TKI was associated with the longest OS. In terms of safety, ICI + Antiangio-Ab was the highest.

[Retracted] Sulforaphane regulates apoptosis­ and proliferation­related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer.

Following the publication of this paper, the authors realized that they had made an error in assembling the data shown in Fig. 6B on p. 2455, and requested the publication of a corrigendum to rectify this error. However, following an independent investigation of the data published in this paper made by the Editorial Office, it was noted that one set of the immunofluorescence assay images shown in Fig. 4A appeared to be strikingly similar to data appearing in different form in a paper published previously in the journal BMC Medicine by different authors at different research institutes [Jing Y­Y, Han Z­P, Sun K, Zhang S­S, Hou J, Liu Y, Li R, Gao L, Zhao X, Zhao Q­D et al: Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK­Mff signaling pathways. BMC Medicine 10: 98, 2012]. Owing to the fact that the abovementioned data in Fig. 4A had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has chosen to decline the authors' request to publish a corrigendum, and decided that this paper should be retracted from the Journal instead. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42: 2447­2458, 2018; DOI: 10.3892/ijmm.2018.3860].

Alpha-fetoprotein-producing advanced colorectal cancer: a rare case report and literature review.

Alpha-fetoprotein(AFP)-producing colorectal cancer is a rare form of colorectal cancer with a high degree of malignancy, advanced stage, strong invasiveness, poor response to treatment, rapid progression, and poor prognosis. Herein, we present the case of a middle-aged (in his 50s) male patient who underwent left neck lymph node biopsy due to "left neck lymph node enlargement for 5 months." Biopsy results revealed metastatic adenocarcinoma, and computed tomography examination of the chest and abdomen suggested a malignant tumor of the sigmoid colon with multiple metastases. Subsequently, the patient underwent colonoscopy, and the pathological result was colonic adenocarcinoma. Regarding tumor markers, serum alpha-fetoprotein (AFP) was 214 ng/mL. The patient received first- and second-line treatments for colon cancer, but progression-free survival was short. AFP was consistently elevated; after 8 months, the patient had AFP levels of 11,371.8 ng/mL, and imaging confirmed disease progression. The patient subsequently died, with an overall survival of more than 9 months. Compared with other tumor markers, AFP better reflects tumor progression in AFP-producing colorectal cancer.

Combination prostate cancer therapy: Prostate-specific membranes antigen targeted, pH-sensitive nanoparticles loaded with doxorubicin and tanshinone.

Prostate cancer is the second most frequently diagnosed cancer in the men population. Combination anticancer therapy using doxorubicin (DOX) and another extract of traditional Chinese medicine is one nano-sized drug delivery system promising to generate synergistic anticancer effects, maximize the treatment effect, and overcome multi-drug resistance. The purpose of this study is to construct a drug delivery system for the co-delivery of DOX and tanshinones (TAN). Lipid nanoparticles loaded with DOX and TAN (N-DOX/TAN) were prepared by emulsification and solvent-diffusion method. PSMA targeted nanoparticles loaded with DOX and TAN (P-N-DOX/TAN) were synthesized by conjugating a PSMA targeted ligand to N-DOX/TAN. We evaluate the performance of this system in vitro and in vivo. P-N-DOX/TAN has a size of 139.7 ± 4.1 nm and a zeta potential of 11.2 ± 1.6 mV. The drug release of DOX and TAN from P-N-DOX/TAN was much faster than that of N-DOX/TAN. N-DOX/TAN presented more inhibition effect on tumor growth than N-DOX and N-TAN, which is consistent with the synergistic results and successfully highlighting the advantages of combing the DOX and TAN in one system. P-N-DOX/TAN achieved higher uptake by LNCaP cells (58.9 ± 1.9%), highest tumor tissue distribution, and the most significant tumor inhibition efficiency. The novel nanomedicine offers great promise for the dual drug delivery to prostate cancer cells, showing the potential of synergistic combination therapy for prostate cancer.

Anaplastic lymphoma kinase (ALK) rearrangement in adult renal cell carcinoma with lung metastasis: a case report and literature review.

Renal cell carcinoma (RCC) with anaplastic lymphoma kinase (ALK) rearrangement is rare, and the genetic profiles of the tumor have not been elucidated. Here, we report a case with recurrent papillary RCC and lung metastasis after nephrectomy for nearly 7 years. The patient first received sunitinib, whereas the drug toxicity was intolerable. Combined Immunohistology (IHC) and fluorescence in situ hybridization (FISH) revealed the patient has an ALK rearrangement, and the patient then was treated with crizotinib. The patient had good tolerance, and a partial response in the target lesions was achieved. In order to further understand the benefit of crizotinib in ALK-rearranged RCC, the patient was detected with whole exome sequencing (WES) to study her genetic profiles. Compared those of RCC cases without ALK rearrangement (nALK-RCC), the patient and nine RCC cases with ALK rearrangement (ALK-RCC) revealed unique genetic characteristics: 1) The common mutations that occurred in RCC were not found in ALK-RCC.; 2) A total of 11 co-existing mutations in ALK-RCC were found, and they occurred in nALK-RCC at a relatively low frequency. DNMT3A mutations were concurrent with ALK fusions in our case. These findings indicated a different genetic alteration pattern of ALK-RCC from nALK-RCC. Our case demonstrated the efficacy of crizotinib in an RCC patient with ALK rearrangement.

Sulforaphane regulates apoptosis- and proliferation­related signaling pathways and synergizes with cisplatin to suppress human ovarian cancer.

Ovarian cancer is currently the most life­threatening type of gynecological malignancy with limited treatment options. Therefore, improved targeted therapies are required to combat ovarian cancer across the world. Sulforaphane is found in raw cruciferous vegetables. The chemotherapeutic and anti­carcinogenic properties of sulforaphane have been demonstrated, however, the underlying mechanisms remain to be fully elucidated, particularly in ovarian cancer. In the present study, the possibility of repurposing sulforaphane as an anti­ovarian cancer agent was examined. Cell viability and colony formation assay were used to test the anticancer efficiency of sulforaphane. Then wound healing assay, migration assay, cell cycle and apoptosis assays were used to detect how the drug worked on the cells. The mechanism of sulforaphane was investigated by western blot analysis. It was found that sulforaphane effectively suppressed the progression of human ovarian cancer cell proliferation, migration and cell cycle, and promoted apoptosis. Sulforaphane inhibited multiple cancer­associated signaling pathways, including B­cell lymphoma 2 (Bcl­2), Bcl­2­associated X protein, cytochrome c, Caspase­3, phosphorylated AKT, phosphorylated nuclear factor­κB, P53, P27, Cyclin­D1 and cMyc, and reduced the expression levels of human epidermal growth factor receptor 2 in human ovarian cancer cells. Sulforaphane synergized with cisplatin to suppress the cancer cell proliferation and enhance ovarian cancer cell apoptosis. Xenograft experiments in vivo confirmed that sulforaphane effectively suppressed tumor growth by inhibiting ovarian cancer cell proliferation through targeting tumor­related signals. The results indicated that sulforaphane may be repurposed as an effective anti­ovarian cancer agent, with further preclinical or clinical investigations required.

[Significance of miR-155, miR-34a and miR-30a expression in diffuse large B-cell lymphoma].

OBJECTIVE: To determine the expressions of miR-155, miR-34a and miR-30a in diffuse large B-cell lymphoma (DLBCL) and to explore their potential correlation with clinicopathological characteristics. METHODS: The expression level of miR-155, miR-34a and miR-30a in 46 DLBCL samples were determined with TaqMan real-time polymerase chain reaction. Interphase fluorescence in situ hybridization (I-FISH) was performed to detect MYC and p53 genes' status, and immunohistochemistry (Envision method) was used to evaluate the expression of CD3, CD10, CD20, BCL-6 and MUM-1 in DLBCL. The DLBCLs were classified into germinal center B cell-like (GCB) and non germinal center B cell-like (non-GCB) subtypes according to Hans' criteria. RESULTS: Compared with normal controls, miR-155 expression level was significantly higher in DLBCL. The expression level of miR-155 in non-GCB type was higher than that in GCB type. It was shown that the patients with MYC rearrangement had lower expression level of miR-155 than the negative controls. Compared with p53 normal group, the expression level of miR-34a was significantly lower in p53 deletion group. It was also shown that the patients with BCL-6 protein expression had lower expression of miR-30a compared with the negative group. CONCLUSION: miR-155 expression level is different in normal controls, DLBCL and patients with subtype DLBCL. It therefore has a diagnosis value for DLBCL. miR-34a is of great prognostic significance. miR-155, miR-34a and miR-30a may be potential therapy targets for DLBCL.

[Correlation of BCL-6, MYC and p53 gene abnormalities with immunological subtypes and prognosis of diffuse large B-cell lymphoma].

OBJECTIVE: To investigate BCL-6, MYC and p53 genes abnormalities in diffuse large B-cell lymphoma (DLBCL) and correlate the result with immunosubtypes and prognosis. METHODS: Interphase fluorescence in situ hybridization (I-FISH) was performed to detect the BCL-6, MYC and p53 genes. Immunohistochemistry (Envision method) was used to measure the expressions of CD3, CD10, CD20, BCL-6, MUM -1, BCL-2 and Ki-67 genes in DLBCL. The patients were classified into germinal center B cell-like (GCB) and non-GCB subtypes according to Hans' algorithm. RESULTS: BCL-6 rearrangement was detected in 10 of 46 DLBCL cases. The presence of gene rearrangement had no correlation with BCL-6 protein expression (P= 0.245). Overall survival (OS, P= 0.138) and progression-free survival (PFS, P= 0.095) were not influenced by BCL-6 rearrangement. All MYC rearrangements were detected in GCB type DLBCL. Deletion of p53 gene was detected in 14 cases and was significantly associated with shorter OS (P= 0.046) and PFS (P= 0.043). CONCLUSION: I-FISH is a rapid, accurate and sensitive method for detecting BCL-6, MYC and p53 abnormalities. No correlation was found between BCL-6 gene rearrangement and BCL-6 protein expression. MYC translocation was more common in GCB type DLBCL compared with non-GCB type ones. Patients with p53 deletion had a poorer prognosis. The p53 gene may provide a useful indicator for the prognosis of DLBCL.

[Influence of 1,25(OH)(2) vitamin D(3) on maturation of human dendritic cells and DC-mediated immune tolerance].

This study was aimed to investigate the effect of 1,25(OH)(2) vitamin D(3) [1,25(OH)(2) Vit D(3)] on the differentiation, maturation and function of human dendritic cells (DC) in vitro and its mechanism. Human peripheral blood mononuclear cells were induced to differentiate to DC in vitro. The DC in test group were cultured with 1,25(OH)(2) Vit D(3) 1 nmol/L for 9 d, while the DC in control group were cultured with the equivalent of absolute alcohol. The expression of co-stimulatory molecules on DC were analyzed by flow cytometry. T cell proliferation induced by DC was assessed by MTT method. The expression of indoleamine 2, 3-dioxygenase (IDO) protein was determined by Western blot. The results showed that compared with the control group, the expression of CD80, CD83 and CD86 on DC in test group was significantly down-regulated (P < 0.05), while the CD1a was up-regulated (P < 0.05). The expression rate of CD80, CD83, CD86, CD1a in test group were (40.43 ± 9.83)%, (20.04 ± 4.73)%, (14.45 ± 5.38)%, (58.48 ± 10.72)% respectively, while in control group were (29.36 ± 13.34)%, (35.91 ± 10.19)%, (27.15 ± 11.64)%, (72.20 ± 12.79)% respectively. Compared with the control group, 1,25(OH)(2) Vit D(3)-treated DC exhibited a markedly reduced ability to stimulate allogenic T cell proliferation and up-regulated IDO protein expression.It is concluded that 1,25(OH)(2) Vit D(3) efficiently inhibits the maturation of DC and DC-mediated T cell proliferation, which may be related to the up-regulation of IDO protein expression.