Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing

Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) and bladder cancer with clinical benefit. Nevertheless, many patients failed to respond to anti-PD-1/PD-L1 treatment, so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy. Here with the data from The Cancer Genome Atlas (TCGA) and our in-house tissue library, PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7 (USP7) in GC. Furthermore, USP7 directly interacted with PD-L1 in order to stabilize it, while abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing

Effect of indirubin-3'-monoxime on proliferation and apoptosis of human HT-29 cells / 中国癌症杂志

Background and purpose: In recent years indirubin-3'-monoxime has been found to be capable of inhibiting some cell proliferation in vitro and in vivo studies, but human colon cancer HT-29 cells, therefore the purpose in this paper was to study the effect of indirubin-3'-monoxime on proliferation and apoptosis of HT-29 cells and its associated mechanism. Methods: HT-29 cells were treated with indirubin-3'-monoxime. The proliferative status of cells was measured by methabenzthiazuron (MTT) assay, flow cytometry (FCM) was used to measure the apoptosis rate. RT-PCR was used to measure the transcription of apoptosis suppressor gene bcl-2, survivin and apoptosis promoting gene Bar. Results: Indimbin-3'-monoxime inhibited growth of HT-29 cells in a dose-dependent and time-dependent manner (F=11.25, P<0.01). The apoptosis rate increased after the treatment by indirubin-3'-monoxime at 10 μmol/L. There were significant differences between different time groups (F=195.25, P<0.01). The transcription of survivin (F=78.75, P<0.01) and Bax (F=87.61, P<0.01) mRNA in HT-29 cells were increased; the transcription of bcl-2 was significantly decreased (F=95.82, P<0.01). Conclusion: Indirubin-3'-monoxime has obviously inhibited proliferation and induce apoptosis of colon cancer HT-29 cells, its mechanism may be related to decrease the bcl-2/Bax ratio.

Comparison of the efficacy and adverse effects of docetaxe or oxaliplatin combined with capecitabine for late-staged gastric cancer in aged patients / 中国综合临床

Objective To compare the short-term efficacy and adverse effects of docetaxe or oxaliplatin combined with capecitabine in the treatment of late-staged gastric cancer in aged patients. Methods Eighty-two aged patients with late-staged gastric cancer were randomly divided into two groups,of which 38 patients were treated group) ,and 44 patients were treated with oxaliplatin (100 mg/m2 ivgtt on 1st day) and eapecitabine (2000 mg/1 cycle). Results There is no failure of follow-up. In the docetaxe group,the effective rate was 52.63% (20/38) and 54.55 % (24/44) for the docetaxe and oxaliplatin group,respectively (P>0.05). The median progression-free survival(PFS) in the docetaxe group (6.1 months) was similar to that in the oxaliplatin group (6.3 months) (P>0.05). Gastrointestinal response,myelosuppression and neurotoxicity (Ⅰ or Ⅱ level) were the most common ad-verse effects observed in both groups (P>0.05). No chemotherapy-related death was observed. Conclusions The short-term efficacy of decetaxe or oxaliplatin combined with capecitabine in the treatment of late-staged gastric cancer in aged patients is similar,and the adverse effects are all within tolerance limits.

Quantity and distribution of CD44+/CD24- cells in breast cancer tissue and the cell lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the distribution and quantity of CD44+/CD24- cells in breast cancer tissue and the cell lines, and as well as its correlation with the expression of various breast cancer markers and molecular subtyping of breast carcinoma.</p><p><b>METHODS</b>The expression of CD44/CD24, estrogen receptor, progesterone receptor, HER2, human estrogen-induced protein PS2, bcl-2 and nm23 in 60 cases of invasive ductal carcinoma of breast were studied by either single or double immunohistochemical staining. The co-expression of CD44 and CD24 in 3 breast cancer cell lines (MCF-7, MDA-MB-468, and MDA-MB-231) was also examined.</p><p><b>RESULTS</b>The quantity and distribution of CD44+/CD24- cells varied greatly and no specific patterns were identified. The percentage of CD44+/CD24- in breast cancer was 65%. The amount of CD44+/CD24- cells did not correlate with the age of patients, lymph node metastasis, tumor size, molecular subtypes and expression of various breast cancer markers in breast carcinoma. The proportion of CD44+/CD24- cells in MCF-7, MDA-MB-468, and MDA-MB-231 cell lines was <1%, 5% and >80%, respectively.</p><p><b>CONCLUSIONS</b>CD44+/CD24- cells are demonstrated in certain breast cancer tissues and cell lines. However, there is no relationship obtained between the quantity or the distribution of these cells and the molecular subtyping or the clinicopathologic parameters in breast cancer.</p>

Expression of nerve growth factor receptors p75 in human bladder carcinoma and its influence by hypoxia / 中华泌尿外科杂志

Objective To explore the expression of the nerve growth factor receptors p75 (p75NGFR) in human bladder carcinoma samples, and the effects of hypoxia on the expression of p75NGFR in human bladder cancer ceils. Methods The expression of p75NGFR in 107 bladder cancer and lymph node specimens were immunohistochemically investigated. The expression of p75NGFR in bladder cancer cell line (T24) was assessed by immunocytochemistry, and reverse tran-scription-PCR in the Normoxic Condition (air, 5%CO2) and in hypoxia condition(10%O2, 5%CO2, 85%N2). Results p75NGFR expressed in 46 of 107(43.0%) tumor samples. There was no signifi-cant correlation between p75NGFR and the factors such as gender, age, extent of the tumors, and pathologic grading(P0.05), p75NGFR was expressed in examined cell line T24, and also expressed in 5 of 24 bladder tumors in metastasized lymph node specimens. Hypoxia markedly down-regulated the expression of p75NGFR of T24 cell line at third day. Conclusions It is suggested that p75NGFR is expressed less in lymph node metastasis. Hypoxia markedly inhibited expression of p75NGFR of T24 cell lines.