Essential amino acids (EAAs) deprivation is a potential antitumor approach because EAAs are critical for tumor growth. To efficiently inhibit tumor growth, continuous deprivation of EAAs is required, ...however, continuous deprivation without precise control will introduce toxicity to normal cells. Herein, a programmable double-unlock nanocomplex (ROCK) was prepared, which could self-supply phenylalanine ammonia-lyase (PAL) to tumor cells for phenylalanine (Phe) deprivation. ROCK was double-locked in physiological conditions when administered systemically. While ROCK actively targeted to tumor cells by integrin αvβ3/5 and CD44, ROCK was firstly unlocked by cleavage of protease on tumor cell membrane, exposing CendR and R8 to enhance endocytosis. Then, hyaluronic acid was digested by hyaluronidase overexpressed in endo/lysosome of tumor cells, in which ROCK was secondly unlocked, resulting in promoting endo/lysosome escape and PAL plasmid (pPAL) release. Released pPAL could sustainably express PAL in host tumor cells until the self-supplied PAL precisely and successfully deprived Phe, thereby blocking the protein synthesis and killing tumor cells specifically. Overall, our precise Phe deprivation strategy effectively inhibited tumor growth with no observable toxicity to normal cells, providing new insights to efficiently remove intratumoral nutrition for cancer therapy.
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In this study, a programmable double-unlock nanocomplex (ROCK) was prepared, which could self-supply phenylalanine ammonia-lyase (PAL) specifically in tumor cells for sustained precise Phe deprivation to mitigate systemic toxicity. The ROCK was sequentially unlocked by protease and hyaluronidase on tumor cell membrane and in tumor cells, respectively. PAL was self-supplied to precisely deprive Phe in the tumor cells, inhibiting tumor growth.
This study addressed whether preoperative chemotherapy (PECT) plus surgery prolongs overall survival (OS) compared with surgery plus postoperative chemotherapy (POCT) among gastric cancer (GC) ...patients in Northwest China.
The authors included 157 GC patients confirmed histologically or by gastroscopic pathological examination treated at the General Hospital of Ningxia Medical University of China between 2012 and 2018. All patients were followed up by telephone in January 2019 within a 2-week period. The endpoint was death due to GC or its complications.
Thirty-eight patients received PECT, 41 patients received POCT, 40 patients received surgery alone, and 38 patients received chemotherapy alone. Surgery was performed with R0 resection and subsequent extended lymph node dissection. Chemotherapy was performed with the S-1, oxaliplatin capecitabine regimen. Patients who received PECT had longer OS than those with POCT treatment (hazard ratio = 2.409,
= 0.037). The 5-year OS rate was 32.7% higher in the PECT group than in the POCT group.
PECT was associated with better OS in GC patients and should be considered by clinicians in GC treatment, although prospective studies are needed for confirmation.
To explore the clinicopathological features and prognostic factors of 734 cases of Chinese Hui and Han patients with adenocarcinoma of the esophagogastric junction (AEG).
In total, 734 patients were ...confirmed to have AEG by gastroscopy and pathology at the General Hospital of Ningxia Medical University between January 2002 and December 2012. Univariate and multivariate analyses of demographic, clinicopathological, and prognostic data were performed.
In total, 734 AEG patients underwent surgical intervention, including 169 Hui patients and 565 Han patients. The male to female ratio was 9.5:1 in Hui patients and 6.4:1 in Han patients, and the average age in both groups was approximately 61 years. The Han patients were more likely to have a cigarette smoking history and an alcohol consumption history than the Hui patients (58.8% vs. 29.4%, p = 0.000; 45.8% vs. 14.6%, p = 0.000). The 5-year survival rate in the Hui and Han patients was 54.3% and 39.9%, respectively (p = 0.024). Age (p = 0.005), sex (p = 0.015), pathologic T stage (p = 0.056), pathologic N stage (p = 0.000), pathologic M stage (p = 0.001), number of resected lymph nodes (p = 0.001) and adjuvant chemoradiotherapy (p = 0.002) were significant independent prognostic factors.
The AEG patients were primarily male and elderly in both Hui and Han groups with the prognosis of Hui patients better than Han patients. Age, sex, pathologic T3-4 stage, pathologic N stage, pathologic M stage, number of resected lymph nodes, and adjuvant chemoradiotherapy were significant independent factors predictive of the prognosis of AEG in both groups.
•The AEG patients were primarily elderly males in both Hui and Han groups.•Han patients had more cigarette smokers and alcohol drinkers than Hui patients.•Most AEG patients were suffered from advanced pathologic stages with poor prognosis.•The prognosis of Hui patients was better than that of Han patients.
Tumor growth and metastasis depend on vessel formation, and inhibition of angiogenesis of tumor by production of anti-angiogenic drugs should be a promising approach for cancer therapy. Tumstatin is ...an angiogenesis inhibitor. The anti-angiogenic activity of tumstatin is localized to the 54–132 amino acids. The gene fragment encoding amino acids 45–132 of tumstatin (tum-5) was subcloned into pcDNA3.1 (pcDNA-tum5). Tum-5 protein could be expressed and secreted in CHO cells after transfection. The conditioned medium (containing tum-5 protein) from the transfectant has an anti-angiogenic effect on HUVEC cells in vitro. The anti-tumor effect of pcDNA-tum5 on mice bearing S180 tumors was evaluated. The results showed that pcDNA-tum-5 has a significant inhibition activity in the growth of the tumors. This study suggests that the gene delivery of tum-5 may be an effective strategy for cancer therapy.
Despite significant developments in its clinical treatment, the reported incidence and mortality of gastric cancer have exhibited marked increases. The molecular mechanisms of gastric cancer ...initiation and progression remain to be fully elucidated. The aim of the present study was to identify novel microRNAs (miRNAs/miRs) with a role in the peritoneal metastasis of gastric cancer by comparing the miRNA expression in the gastric cancer cell line GC9811 with that in its variant GC9811-P, a sub-cell line with a high potential for peritoneal metastasis. A miRNA microarray analysis identified 153 dysregulated miRNAs, including 74 upregulated and 79 downregulated miRNAs. Of these, four significantly upregulated miRNAs (miR-181a-5p, miR-106b-5p, miR-199a-3p and miR-148a-3p) and four downregulated miRNAs (miR-146a-5p, miR-21-5p, miR-222-3p and miR-221-3p) were selected and further confirmed by reverse transcription-quantitative polymerase chain reaction analysis. Furthermore, knockdown of miR-21-5p promoted the migration and invasion of GC9811 cells. Collectively, the results suggested that the miRNA expression profile in GC9811-P vs. GC9811 cells was altered to favor disease progression, and the dysregulated miRNAs, including miR-21-5p, may therefore provide novel biomarkers and potential therapeutic targets for gastric cancer metastasis.
Gastric cancer is a type of cancer with increasing incidence and high mortality rates, but molecular biomarkers of diagnostic and therapeutic value are currently lacking. The aim of the present study ...was to examine the expression pattern of the interleukin 1 receptor-like 1 (ST2) protein and assess its clinicopathological significance in gastric cancer. Western blot analysis of 12 gastric cancer specimens and paired adjacent tissues demonstrated that the protein levels of 2 isoforms of ST2, soluble secreted ST2 and the ST2 variant without the third immunoglobulin motif and splicing in the C-terminal, were markedly decreased in cancer tissues compared with non-cancerous tissues. Immunohistochemical analysis demonstrated that ST2 protein expression was markedly decreased in primary gastric cancer tissues (39.1%, 90/230) compared with adjacent non-cancerous tissues (60.7%, 54/89) (P<0.05). Statistical analysis demonstrated that decreased ST2 expression was significantly associated with advanced tumor node metastasis stage (P<0.001) and tumor differentiation (P<0.001). These data suggest that ST2 protein may be a valuable biomarker of gastric cancer progression and pathogenesis.
Background
Recently, we identified the esophageal carcinoma related gene 4 (
ECRG4
) as a novel candidate tumor suppressor gene and a promising therapeutic target in nasopharyngeal carcinoma (NPC). ...In addition, we found that reduced ECRG4 expression in NPC was associated with promoter hypermethylation. The aim of the current study was to assess the expression status of the ECRG4 protein in breast cancer and to clarify its clinicopathological significance and potential prognostic implications.
Methods
Western blotting was used to examine ECRG4 protein levels in 20 paired breast cancer tissues and adjacent noncancerous tissues. In addition, we performed ECRG4 immunohistochemistry on 113 clinicopathologically well-characterized breast cancer samples and assessed putative associations between its expression and overall patient survival rates.
Results
We found that ECRG4 protein expression was significantly reduced in the breast cancer tissues compared to the noncancerous tissues. Clinicopathological analyses revealed that loss of ECRG4 protein expression, observed in 41.6 % (47/113) of the primary breast cancer tissues tested, was significantly correlated with lymph node metastasis (
P
= 0.026), advanced tumor stage (
P
= 0.042) and unfavorable overall survival (
P
= 0.004). Additional multivariate analyses revealed that ECRG4 protein expression may serve as an independent prognostic factor for the prediction of patient survival (
P
= 0.033).
Conclusion
Our data suggest that loss of ECRG4 protein expression may be involved in tumor progression and may serve as a prognostic biomarker for breast cancer.
Background
Human nasopharyngeal carcinoma (NPC) is a malignant type of cancer with an increasing incidence. As yet, however, molecular biomarkers with a strong diagnostic impact and a major ...therapeutic promise have remained elusive. Here, we identified the esophageal carcinoma related gene 4 (
ECRG4
) as a novel candidate tumor suppressor gene and a promising therapeutic target for NPC.
Methods
RT-PCR, Western blotting, methylation-specific PCR and bisulfite sequencing were performed to assess the expression and methylation status of the
ECRG4
gene in primary NPC samples, NPC-derived cell lines and patient-derived peripheral blood samples. The NPC-derived cell line CNE1 was selected for treatment with a methylation inhibitor to restore
ECRG4
expression. In addition, cell proliferation, invasion and colony formation assays were performed to assess the inhibitory effects of exogenous
ECRG4
expression in CNE1 cells.
Results
Down-regulated
ECRG4
expression was found to occur in 82.5 % (33/40) of the primary NPC biopsies tested. This down-regulation was significantly correlated with its tumor-specific promoter methylation status (72.5 %, 29/40) and was also observed in the matching peripheral blood samples from the NPC patients (57.5 %, 23/40). Pharmacologic demethylation through 5-aza-dC treatment led to gene reactivation in
ECRG4
methylated and silenced NPC cell lines. Moreover, exogenous expression of
ECRG4
in the CNE1 cell line strongly inhibited its growth and invasive capacities, as well as its enhanced chemosensitivity to cisplatin through autophagy induction.
Conclusion
Our data suggest that methylation-mediated suppression of the
ECRG4
gene occurs frequently in NPC and that restoration of its expression may have therapeutic benefits.
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