Efficacy and safety of regorafenib or fruquintinib plus camrelizumab in patients with microsatellite stable and/or proficient mismatch repair metastatic colorectal cancer: an observational pilot study.

This study was to investigate the efficacy and safety of regorafenib or fruquintinib combined with camrelizumab in patients with microsatellite stable (MSS) and/or proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC). Medical records of MSS/pMMR mCRC patients who received regorafenib (80 mg) or fruquintinib (3 mg) once a day (21 days on/7 days off) plus camrelizumab (200 mg) every three weeks in Yuhuangding Hospital between January 2020 and June 2020 were retrospectively collected. Follow-up data up to November 1st, 2020 was gathered. The primary endpoint was the objective response rate (ORR) and disease control rate (DCR). The safety profile was the secondary endpoint. A total of 16 patients were enrolled. The ORR was 25.0% (4/16) and the DCR was 62.5% (10/16). The main adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (81.3%), fatigue (43.8%), hypertension (37.5%), hand-foot skin reaction (25.0%), and thyroid dysfunction (25.0%). Most AEs were grade 1 or 2, with only 1 patient of grade 3 liver dysfunction. All the AEs were ameliorated by effective symptomatic treatment. Regorafenib or fruquintinib plus camrelizumab exhibited promising efficacy in patients with MSS/pMMR mCRC. The toxicity was moderate and manageable.

LncRNA AWPPH and miRNA-21 regulates cancer cell proliferation and chemosensitivity in triple-negative breast cancer by interacting with each other.

Long-non-coding RNAs (lncRNA) AWPPH promotes the progression of liver and bladder cancer, indicating its oncogenic role. The current study aimed to explore the involvement of AWPPH in triple-negative breast cancer (TNBC). In the current study, we found that plasma levels of lncRNA AWPPH and microRNA-21 (miRNA-21) were upregulated in patients with TNBC than in healthy controls, and the upregulation of plasma lncRNA AWPPH and miRNA-21 distinguished early-stage patients with TNBC from healthy controls. Plasma levels of lncRNA AWPPH and miRNA-21 were significantly and positively correlated in both patients with TNBC and healthy controls. LncRNA AWPPH and miRNA-21 overexpression led to promoted cancer cells proliferation and improved cancer cell viability under carboplatin treatment, while lncRNA AWPPH small interfering RNA (siRNA) silencing played an opposite role. In addition, miRNA-21 overexpression attenuated the effects of lncRNA AWPPH siRNA silencing on of cancer cell behaviors. LncRNA AWPPH overexpression led to upregulated miRNA-21 in TNBC cells, while miRNA-21 overexpression also led to significantly upregulated lncRNA AWPPH expression. Therefore, lncRNA AWPPH and miRNA-21 may regulate cancer cell proliferation and chemosensitivity in TNBC by interacting with each other.

Knockdown of LINC01614 inhibits lung adenocarcinoma cell progression by up-regulating miR-217 and down-regulating FOXP1.

We tried to identify the function of LINC01614 in lung adenocarcinoma (LUAD) and reveal its underlying mechanisms. qRT-PCR was applied to assess the expression of LINC016014 in LUAD tissues, noncancerous tissues and cells. Through colony formation assay, MTT assay and apoptosis analysis, we examined the variation of cell proliferation and apoptosis ability after silencing LINC01614. Moreover, the targeting interactions among LINC01614, miR-217 and FOXP1 were validated via luciferase reporter assay, and then, we regulated the expression of miR-217 and FOXP1 to ascertain their importance in cell proliferation and apoptosis. LINC01614 and FOXP1 were found to be up-regulated in LUAD tumours and cells, whereas miR-217 was down-regulated. The experiment showed that target-specific selectivity exists between LINC01614-miR-217 and miR-217-FOXP1 3'UTR. Furthermore, we disclosed that inhibition of LINC01614 could activate miR-217, which subsequently restrained FOXP1. It was proved that LINC01614 promoted FOXP1 by inhibiting miR-217, which ultimately stimulated the development of LUAD.

Analysis of the differences of serum protein mass spectrometry in patients with triple negative breast cancer and non-triple negative breast cancer.

The objective of the present study was to investigate differences of serum protein mass spectrometry in patients with triple negative breast cancer (TNBC) and non-TNBC and thus to search for candidate serum protein biomarkers for identification and diagnosis of TNBC. Thirty serum samples from patients with TNBC without any treatment and 30 serum samples from patients with non-TNBC without any treatment were detected by using two-dimensional gel electrophoresis and matrix-assisted laser dissociation tandem time-of-flight mass spectrometry (MALDI-TOF-MS). PDQest 7.0 software of Bio-Rad was adopted to screen differentially expressed proteins. Protein ID retrieval was conducted by using Mascot software to confirm the results of differential proteins. Two-dimensional gel electrophoresis profiles were obtained successfully. A total of 16 differential protein loci were discovered by analyzing patient sera of the two groups using two-dimensional gel electrophoresis analysis software. Ten differential proteins were identified by mass spectrometric analysis in the 16 differential proteins. Combined with database and literature search results, it is speculated that the specifically upregulated proteins and downregulated proteins including transthyretin, haptoglobin, and antitrypsin may be the potential markers for early diagnosis of TNBC. Comparing the TNBC patients with the non-TNBC patients, there are differences in serum protein compositions. The ten differential proteins discovered in the present study provide reference basis for further improving early diagnosis and identification and diagnosis index of TNBC. Especially, transthyretin, haptoglobin, and antitrypsin show dramatic significances for the early diagnosis of TNBC.

Clinicopathologic characteristics and prognostic factors in patients with operable HER-2 overexpressing breast cancer.

OBJECTIVE: To study the relationship between clinical pathologic characteristics, treatment modalities and prognostic factors in HER-2 (Human Epidermal growth factor Receptor-2) overexpressed breast carcinoma. MATERIALS AND METHODS: Major clinico-pathological factors including therapeutic modalities and survival status of 371 breast cancer patients with HER2 over-expression, teated at Yantai Yuhuangding Hospital from March of 2002 to December of 2010 were retrospectively studied, with special attention focused on survival-related factors. RESULTS: The median age of the total 371 patients in this study was 48 years at time of diagnosis, among which, the leading pathological type was infiltrating ductal carcinoma (92.5%); 62.8% presented with a primary tomor larger than 2 cm in diameter at diagnosis, 51.0% had axillary lymph node (ALN) metastases; ER (Estrogen receptor) /PR (Progesterone receptor) double negative occured in 52.8% of cases, and PCNA (proliferation cell nuclear antigen) (+ + +) was found in 55.1%. HER-2 overexpressed patients were usually in advanced stage when the diagnosis was made (72.8% at stages IIA~IIIC). The prognosis and survival were assessed in 259 patients with complete follow-up data. 5-year DFS (disease-free survival) and OS (overall survival) rate was 68.0% and 78.0% respectively. Univariate analysis revealed that age, tumor size, ALN metastases, LVSI (lymph-vascular space involvement), PCNA status, hormonal therapy, chemotherapy cycles, and HER-2 overexpression, correlated closely with the prognosis. ALN metastases, LVSI, PCNA status and chemotherapy cycles were independent predictors of survival. CONCLUSIONS: HER-2 overexpressed breast cancer has special clinical and pathological characteristics, with advanced clinical stages and high rate of ER/PR double negative. Lymph node metastases, LVSI, PCNA and chemotherapy cycles are independent predictors of prognosis.

Long-term outcomes of gemcitabine and cisplatin in patients with recurrent or metastatic esophageal squamous cell carcinoma: a phase II trial.

BACKGROUND: Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Prior studies had demonstrated potential synergistic antitumor activity of gemcitabine in combination with cisplatin. Therefore, we studied the efficacy and tolerability of such combination for esophageal cancer. METHODS: Between October 2003 and October 2006, thirty-eight patients with metastatic or recurrent advanced squamous cell carcinoma of the esophagus were enrolled. The median number of treatment cycles per patient was 4 (range 1 - 7). Gemcitabine was given at 1000 mg/m(2) over 30 minutes on days 1, 8 and cisplatin 40 mg/m2 was given on days 1, 2 in an every 21-day cycle. RESULTS: The median follow-up for all 38 patients was 76 months (range 11 - 88 months). The overall response rate was 42.1% (95%CI, 25.5% - 56.5%). Median progression-free survival and median survival for all patients were 4.1 months (95%CI, 3.0 - 5.7 months) and 10 months (95%CI, 7 - 12 months), respectively. Patients with a response had significantly longer median survival compared with the patients without a response (11 months vs. 7.5 months, P = 0.0069). Overall survival at 1 year was 36.8%, at 2 years was 10.5%, and at 5 years was 5.3%. The most common grade 3 - 4 toxicity for all patients was leucopenia (44.7%). CONCLUSIONS: This cisplatin-gemcitabine regimen was manageable and had significant efficacy in patients with esophageal squamous cell carcinoma. Patients with a response had improved survival time. Furthermore, a small number of the patients with metastatic esophageal cancer were still alive in 5 years with this regimen.

[Responses of advanced esophageal cancer to chemotherapy and prognostic factors: a report of 138 cases].

BACKGROUND & OBJECTIVE: The prognosis of advanced esophageal cancer is poor. There are no definite prognostic factors and standard regimens for these patients. This study was to analyze the responses of advanced esophageal cancer to chemotherapy, and explore its probable prognostic factors. METHODS: Clinical data of 138 naïve patients with histologically or pathologically confirmed advanced esophageal cancer, treated from Dec. 1984 to Apr. 2006 in Cancer Hospital of Chinese Academy of Medical Sciences, were analyzed using Chi-square test, Kaplan-Meier method, and log-rank test. Of the 138 patients, 68 were treated with taxol or gemcitabine or oxaliplatin (new drug group), including 64 (94.1%) treated with cisplatin; 70 were treated without taxol, gemcitabine and oxaliplatin (conventional drug group), including 48(68.6%) treated with cisplatin. RESULTS: The response rate of 138 patients was 47.8%. The median time to progression (TTP) was 4 months; the median survival time was 10 months. The response rate was significantly higher in new drug group than in conventional drug group (58.8% vs. 37.1%, P=0.011). Univariate analysis indicated that age, hemoglobin (HB) level before treatment, chemotherapy cycles, short-tem efficacy, TTP and therapeutic methods were significant prognostic factors. Cox multivariate regression analysis showed that TTP, therapeutic methods and HB level before treatment were independent prognostic factors. CONCLUSIONS: Taxol or gemcitabine combined cisplatin has certain effect on advanced esophageal cancer. TTP, therapeutic methods and HB level before treatment are independent prognostic factors of this disease.