Wilkinsjacobson2076
P16 methylation is expected to be potential diagnostic and therapeutic targets for esophageal cancer (EC). The intratumoral heterogeneity (ITH) of EC has been mentioned but has not been quantitatively measured yet. We aimed to clarify the impact of ITH on pathological diagnosis and P16 methylation, and the concordance between endoscopic biopsy and the corresponding surgically resected tissue.
We designed a systematic sampling method (SSM) compared with a general sampling method (GSM) to obtain EC tumor tissue, tumor biopsy, and normal squamous epithelium biopsy. MethyLight assay was utilized to test P16 methylation. All specimens obtained by the SSM were pathologically diagnosed.
A total of 81 cases were collected by the GSM, and 91.4% and 8.6% of them were esophageal squamous cell carcinomas (ESCCs) and esophageal adenocarcinomas (EADs), respectively. Nine SSM cases were 100.0% ESCCs. The positive rates of P16 methylation of the GSM tumor and normal tissues were 63.0% (51/81) and 32.1% (26/81), respectively. For SSM samples, tumor tissues were 100.0% (40/40) EC and 85.0% (34/40) P16 methylated; tumor biopsy was 64.4% (29/45) diagnosed of EC and 68.9% P16 methylated; the corresponding normal biopsies were 15.7% (8/51) dysplasia and 54.9% (28/51) P16 methylated. The concordance of pathological diagnosis and P16 methylation between tumor biopsy and the corresponding tumor tissue was 75.0% and 62.5%, respectively.
The SSM we designed was efficient in measuring the ITH of EC. We found inadequate concordance between tumor biopsy and tissue in pathological diagnosis and P16 methylation.
The SSM we designed was efficient in measuring the ITH of EC. We found inadequate concordance between tumor biopsy and tissue in pathological diagnosis and P16 methylation.
Gallbladder cancer (GBC) is a malignant cancer with poor prognosis. Evidences have shown that miRNAs are closely related to the occurrence of GBC; thus, we aimed to explore miRNAs, which plays an important role in the occurrence and development of GBC.
Microarray analysis was performed to investigate the differentially expressed miRNAs between five non-neoplastic gallbladder tissues (normal tissues) and five gallbladder tumor tissues (tumor tissues). RT-qPCR was performed to detect the level of miR-181b-5p in cells, and CCK-8 was performed to detect cell viability. Then, glucose assay kit or lactic acid assay kit was performed to detect the level of glucose consumption or lactate production. Next, transwell and wound healing assays were used to assess cell migration. In addition, dual-luciferase reporter assay was used to verify the relationship between miR-181b-5p and PDHX. At last, Western blotting was performed to determine the protein level of PDHX.
Microarray analysis suggested miR-181b-5p was sign GBC by upregulating PDHX under hypoxia. This finding suggested that miR-181b-5p might be considered as a novel therapeutic target for the treatment of GBC.
Co-mutations was associated with poor response to EGFR-TKIs. First-generation EGFR-TKIs combined with chemotherapy was reported to be more effective than TKIs alone in advanced lung adenocarcinoma patients.
This retrospective study aimed to explore whether
-mutant patients with co-mutations can benefit from EGFR-TKIs plus chemotherapy.
We retrospectively collected data of 137
-mutant patients with advanced lung adenocarcinoma who underwent next-generation sequencing in our hospital in 2018. Among them, 96 were treated with EGFR-TKIs alone and 41 received EGFR-TKIs plus chemotherapy. We analyzed the progression-free survival (PFS) of patients with co-mutations using different treatments.
Concurrent
mutations, especially exon 4 and 6, were associated with a markedly shorter time to progression on EGFR-TKI monotherapy (11.4 months
. 16.6 months,
=0.003), while EGFR-TKIs plus chemotherapy would benefit those patients more (with
11.4 months
. 19.1 months,
=0.001, HR=0.407; without
16.6 months
. 18.9 months,
=0.379, HR=0.706). The incidence of T790M after resistance was equal in patients treated with different treatments (53%
. 53%,
=0.985).
In our study, concurrent
mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.
In our study, concurrent TP53 mutations were found to be risk factors for EGFR-TKI monotherapy, but TKI combined with chemotherapy could eliminate this heterogeneity.Ovarian cancer is the most common and aggressive type of tumor of the female reproductive system. Two factors account for this detrimental clinical presentation (i) the lack of early detection methods and (ii) the inherently aggressive nature of this malignancy. Currently, transcriptomic analyses have become important tools to identify new targets in different cancer types. In this study, by measuring expression levels in ovarian cancer samples and stem cell samples, we identified 24 tumor suppressor genes consistently associated with poor prognosis. Combined results further revealed a potential therapeutic candidate, BTG2, which belongs to the antiproliferative gene family. Our results showed that BTG2 expression regulated ovarian cancer cell proliferation via G1/S phase cell cycle arrest by regulating Cyclin D1, CDK4, p-AKT, and p-ERK expression. BTG2 also inhibited cell migration by modulating MMP-2 and MMP-9 expression. Furthermore, xenograft models confirmed a growth inhibitory effect of BTG2 in ovarian cancer in vivo. BTG2 was significantly associated with ovarian cancer FIGO stage and grade in the clinic. Our findings indicated that BTG2 exerts a suppressive impact on ovarian cancer and could be a potential biomarker.Long-term endocrine treatment which results in estrogen deprivation causes chronic stress associated with a series of uncomfortable symptoms leading not only to a decrease in quality of life but also to cancer recurrence, which may be mediated primarily through the enhanced expression of angiogenic factors, as well as a series of inflammatory microenvironmental changes that favor tumor progression. In this study, we designed a clinical trial and aimed to explore the effects of Sanhuang Decoction (SHD) treatment on chronic stress, inflammatory factors, and breast cancer recovery. A total of 90 patients with breast cancer who met the inclusion/exclusion criteria were randomly allocated to a treatment or control group. The treatment group received the standard endocrine treatment and the traditional Chinese medicine decoction known as SHD. The control group received the standard endocrine treatment only. The treatment period was 6 months. The modified Kupperman Menopausal Index, the self-rating anxiety scale, anrolled tumor growth and prevented drug resistance.
Chinese Clinical Trial Registry, identifier ChiCTR-IIR-2000041413. Date of registration 2017-06-07 (retrospective registration).
Chinese Clinical Trial Registry, identifier ChiCTR-IIR-2000041413. Date of registration 2017-06-07 (retrospective registration).The components of the immune system play a very sincere and crucial role in combating tumors. However, despite their firm efforts of elimination, tumor cells cleverly escape the surveillance process by adopting several immune evasion mechanisms. The conversion of immunogenicity of tumor microenvironment into tolerogenic is considered as a prime reason for tumor immune escape. Therapeutically, different immunotherapies have been adopted to block such immune escaping routes along with better clinical outcomes. Still, the therapies are haunted by several drawbacks. Over time, curcumin has been considered as a potential anti-cancer molecule. Its potentialities have been recorded against the standard hallmarks of cancer such as continuous proliferation, escaping apoptosis, continuous angiogenesis, insensitivity to growth inhibitors, tissue invasion, and metastasis. Hence, the diversity of curcumin functioning has already been established and exploration of its application with immunotherapies might open up a new avenue for scientists and clinicians. In this review, we briefly discuss the tumor's way of immune escaping, followed by various modern immunotherapies that have been used to encounter the escaping paths and their minute flaws. Finally, the conclusion has been drawn with the application of curcumin as a potential immune-adjuvant, which fearlessly could be used with immunotherapies for best outcomes.Immunosuppressive molecules are valuable prognostic biomarkers across different cancer types. Leukocyte immunoglobulin like receptor subfamily B1 (LILRB1) is considered to be an immunosuppressive molecule, which is an important receptor of human leukocyte antigen G. However, the clinical significance of LILRB1 expression in gastric cancer remains unexplored. We analyzed the immunohistochemistry data of 166 gastric cancer patients to determine the clinicopathologic and survival significance of LILRB1. Immunofluorescence was conducted to detect the co-localization of LILRB1 with infiltrating immune cells. Additionally, we also assessed the immune contexture, immune cell functions and tumor microenvironment state related to LILRB1. We found that LILRB1 was mainly present in tumor stroma which was higher in tumor tissues compared with matched adjacent tissues. High-LILRB1 expression was associated with more advanced tumor stage, higher recurrence risk and worse survival. Immunohistochemistry and bioinformatic analysis showed that LILRB1 had a significant positive correlation with M2 tumor-associated macrophages (TAMs) infiltration. Immunofluorescence confirmed that M2 TAMs were the primary immune cells expressing LILRB1. Dense infiltration of LILRB1+ M2 TAMs yielded an immunosuppressive microenvironment manifested as enriched exhausted CD8+ T cells and increased immunosuppressive cytokines. Moreover, patients with high infiltration of both LILRB1+ cells and M2 TAMs indicated poor prognosis and inferior therapeutic responsiveness to adjuvant chemotherapy. In conclusion, LILRB1+ M2 TAMs were associated with a pro-tumor immune contexture and determine poor prognosis in gastric cancer. Further studies are essential to explore therapeutic targeting LILRB1+ M2 TAMs.The dysregulation of epigenetic modification and energy metabolism cooperatively contribute to the tumorigenesis of nasopharyngeal carcinoma (NPC). However, the detailed mechanisms underlying their joint contribution to NPC development and progression remain unclear. Here, we investigate the role of Acy1 Coenzyme A Acyltransferases1 (ACAT1), a key enzyme in the metabolic pathway of ketone bodies, in the proliferation and metastasis of NPC and to elucidate the underlying molecular mechanisms. Ketogenesis, plays a critical role in tumorigenesis. Previously, we reported two enzymes involved in ketone body metabolism mediate epigenetic silencing and act as tumor suppressor genes in NPC. Here, we identify another key enzyme, Acetyl-CoA acetyltransferase 1 (ACAT1), and show that its transcriptional inactivation in NPC is due to promoter hypermethylation. Ectopic overexpression of ACAT1 significantly suppressed the proliferation and colony formation of NPC cells in vitro. The migratory and invasive capacity of NPC cells was inhibited by ACAT1.
