Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review.

BACKGROUND: Colorectal cancer (CRC) is the third most frequent and the second most fatal cancer. The search for more effective drugs to treat this disease is ongoing. A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies. Ubiquitin-specific peptidases (USPs), the largest group of the deubiquitinase protein family, have long been implicated in various cancers. There have been numerous studies on the role of USPs in CRC; however, a comprehensive view of this role is lacking. AIM: To provide a systematic review of the studies investigating the roles and functions of USPs in CRC. METHODS: We systematically queried the MEDLINE (via PubMed), Scopus, and Web of Science databases. RESULTS: Our study highlights the pivotal role of various USPs in several processes implicated in CRC: Regulation of the cell cycle, apoptosis, cancer stemness, epithelial-mesenchymal transition, metastasis, DNA repair, and drug resistance. The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC. The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms. CONCLUSION: Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

Comparison of induction therapy in non-high risk acute promyelocytic leukemia with arsenic trioxide or in combination with ATRA.

BACKGROUND: Acute promyelocytic leukemia (APL) is a curable form of acute myeloid leukemia; in recent years, the use of new treatment strategies, such as combination therapy, have led to improved APL outcomes. Here, outcomes of patients treated with a combination of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are compared against patients treated with single ATO therapy. PATIENTS AND METHODS: In total, 67 patients with non-high-risk APL were evaluated. A group of 30 patients received ATO, and another group of 37 patients received ATO plus ATRA. ATO infusion at a dose of 0.15 mg/kg/day was continued till complete remission was achieved or till 60 days of consumption, and after 28 days of rest, second ATO course was initiated for 28 days as consolidation. Four courses separated by 28-day rest were planned. In the second group, 45 mg/m2/day ATRA was added to ATO protocol. RESULTS: All patients except one in the ATO group and all patients in the ATO plus ATRA group were alive after a median follow-up of 18 and 17 months, respectively; 2.5-year overall survival in the ATO group was 86% (p-value = .32). Five patients in the ATO group experienced relapse, and 2.5-year leukemia-free survival in this group was 60%. No relapse occurred in the ATO plus ATRA group (p-value = .01). Differences in the mean of white blood cell (p-value = .67), platelet (p-value = .15), liver (p-value = .37), and renal (p-value = .95) dysfunctions were not significant. CONCLUSION: Although ATO has been considered a first-line therapy in patients with APL, several studies have reported improved outcomes with a combination of ATO plus ATRA. This study demonstrated a significant decrease in relapse with this combination compared with single ATO therapy and supported the importance of ATRA in APL treatment.

The outcomes of esophageal and gastric cancer treatments in a retrospective study, single center experience.

INTRODUCTION: Esophageal and gastric cancers are among the most common cancers in Iran. Usually survival of these cases is poor despite of treatment. Here we studied outcome of these cases in our center to have an estimation of general prognosis of patients. METHODS: In this retrospective study, we reviewed the data of patient's files before treatment, including cancer stage at diagnosis, types of treatments and outcomes. We studied 368 patients treated between 1995 and 2011. RESULTS: The study included 368 patients (248 [67.4%] males and 120 [32.6%] females) with a median age of 58 (range: 23 - 94). Sixty nine patients (18.8%) had esophageal cancer with a median age of 58.5 years (range: 33 - 84), and 47.8% (33/69) of whom were male. Sixty five (17.7%) were reported to have gastro-esophageal junction (GEJ) with a median age of 62.0 (range: 32 - 94), among them 72.3% (47/65) of whom were male and finally Two hundred thirty four (63.6%) had gastric cancer with a median age of 57.0 (range: 23 - 82), which 71.8% (168/234) of whom were male. The Median follow-up was 10 months. The majority of patients were diagnosed at an advanced stage of disease. Stage III or IV was observed in 65.0% (39/60) of patients with esophageal cancer, 75.0% (33/44) with GEJ cancer and 65.4% (121/185) with gastric cancer. In this study, 58% of patients with esophageal cancer, 50.8% with GEJ and gastric cancers had unresectable disease or metastases at presentation. One-year EFS was 51.8% (95% CI: 39.8 - 67.3%), 32.8% (95% CI: 22.1 - 48.7%), and 56.7% (95% CI: 50.1 - 64.3%) in patients with esophageal, GEJ and gastric cancers, respectively (p = 0.002). The 1-year OS was 54.5% (95% CI: 42.6 - 69.8%), 39.5% (95 CI: 28.1 - 55.5%), and 68.2% (95% CI: 61.8 - 75.3%), respectively (p < 0.001). CONCLUSION: Cancers of the upper gastrointestinal (GI) tract contribute to the high mortality and morbidity rates because they are more likely to be diagnosed at late or advanced stages of disease. Cancer of the GEJ has a poor prognosis compared to esophageal and gastric cancers. Moreover, treatment protocols may need improvement to achieve better results.