Chaperone-mediated autophagy degrade Dicer to promote breast cancer metastasis.

Metastasis in breast cancer usually lead to the majority of deaths on clinical patients. Accordingly, diagnosis of metastasis at the early stage in breast cancer is important to improve the prognosis. We observed that Dicer protein levels are significant decrease in highly invasive breast cancer cells and usually correlated with poor clinical outcomes. Following, we aim to clarify the molecular regulatory mechanism of this phenomenon in breast cancer to provide a new therapeutic target. In this study, we obtained that Dicer expression correlated with metastasis and invasion without affect cell stability in breast cancer cells. Importantly, we identified the regulatory mechanism of Dicer protein degradation, the chaperone-mediated autophagy (CMA)-mediated degradation that is major mechanism to decrease Dicer protein expression and lead to cancer metastasis. We discovered that heat shock cognate 71-kDa protein (Hsc70) which as a CMA-related factor interacts with the CMA-targeting motif I333A/K334A on Dicer to promote degradation through CMA. Taken together, our findings hint that Dicer highly correlated with cancer metastasis, we reveal the tumor-promoting effect of CMA-mediated Dicer degradation in breast cancer.

ERK-mediated transcriptional activation of Dicer is involved in gemcitabine resistance of pancreatic cancer.

Gemcitabine has been a commonly used therapeutic agent for treatment of pancreatic cancer. In the clinic, a growing resistance to gemcitabine has been observed in patients with pancreatic cancer, and investigation of the underlying mechanism of gemcitabine resistance is urgently required. The microRNA (miRNA)-producing enzyme, Dicer, is crucial for the maturation of miRNAs, and is involved in clinical aggressiveness, poor prognosis, and survival outcomes in various cancers, however, the role of Dicer in acquired gemcitabine resistance of pancreatic cancer is still not clear. Here, we found that Dicer expression was significantly increased in gemcitabine-resistant PANC-1 (PANC-1/GEM) cells compared with parental PANC-1 cells and observed a high level of Dicer correlated with increased risk of pancreatic cancer. Suppression of Dicer obviously decreased gemcitabine resistance in PANC-1/GEM cells; consistently, overexpression of Dicer in PANC-1 cells increased gemcitabine resistance. Moreover, we identified that transcriptional factor Sp1 targeted the promoter region of Dicer and found ERK/Sp1 signaling regulated Dicer expression in PANC-1/GEM cells, as well as positively correlated with pancreatic cancer progression and suggest that targeting the ERK/Sp1/Dicer pathway has potential therapeutic value for pancreatic cancer with acquired resistance to gemcitabine.

AXL is crucial for E1A-enhanced therapeutic efficiency of EGFR tyrosine kinase inhibitors through NFI in breast cancer.

AXL which is a chemosensitizer protein for breast cancer cells in response to epidermal growth factor receptor-tyrosine kinase inhibitor and suppresses tumor growth. The clinical information show nuclear factor I (NFI)-C and NFI-X expression correlate with AXL expression in breast cancer patients. Following, we establish serial deletions of AXL promoter to identify regions required for Adenovirus-5 early region 1A (E1A)-mediated AXL suppression. All of the NFI family members were extensively studied for their expression and functions in regulating AXL. Moreover, E1A post-transcriptionally downregulates AXL expression through NFI. NFI-C and NFI-X, not NFI-A and NFI-B, resulting in cell death in response to EGFR-TKI. Our finding suggests that NFI-C and NFI-X are crucial regulators for AXL and significantly correlated with poor survival of breast cancer patients.

Long-term and short-term surgical outcomes of single-incision laparoscopic hepatectomy on anterolateral liver segments.

BACKGROUND: Laparoscopic liver resection yields improved short-term surgical outcomes, whereas the reports about clinical benefits of single-incision laparoscopic hepatectomy (SILH) are scarce. This retrospective study is to compare the surgical outcomes of SILH with those of multi-incision laparoscopic hepatectomy (MILH). METHODS: The study included 54 patients who had undergone SILH and 184 patients who had undergone MILH between January 2010 and December 2017. Short-term outcomes were compared in those of patients who underwent left lateral sectionectomy and partial hepatectomy of segment 5-6. A subgroup analysis of hepatocellular carcinoma (HCC) was also performed for long-term outcome comparisons. RESULTS: In those of patients who underwent left lateral sectionectomy, SILH group had less chronic hepatitis B (15.2 vs. 45.8%; p = 0.004), less liver cirrhosis (12.1 vs. 50.0%; p = 0.002), less tumor proximal to major vessel (6.1 vs. 29.2%; p = 0.018), shorter surgical time (113.2 ± 37.9 vs. 146.0 ± 50.5 min; p = 0.007), and shorter postoperative hospital stays (4.4 ± 1.1 vs. 5.4 ± 1.3 days; p = 0.002) compared with MILH group. In those of patients with tumor located at segment 5-6, no significant differences were observed in surgical time, blood loss, complications, and mortality. Single-incision laparoscopic partial hepatectomy was only associated with wider surgical margins (11.8 ± 7.0 vs. 5.3 ± 5.2 mm; p = 0.003). In the HCC subgroup, SILH had similar 1-, 3-, and 5-year overall survival and 1-, 3-, and 5-year recurrence-free survival rates compared with patients who had undergone MILH. CONCLUSIONS: The study demonstrates the safety and feasibility of single-incision laparoscopic liver resection for left lateral sectionectomy and partial hepatectomy for segment 5-6. In selected patients within the group and by experienced surgical team, the SILH technique results in comparable short-term surgical outcomes and long-term oncological outcomes.

Long-term and short-term surgical outcomes of laparoscopic versus open liver resection for hepatocellular carcinoma: might laparoscopic approach be better in early HCC?

BACKGROUND: This retrospective study compared the short- and long-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) and identified patients who might gain more benefits from LLR. METHODS: The demographic and perioperative data, short-term surgical outcomes, and long-term oncological results of all 313 patients who received elective liver resection for hepatocellular carcinoma (HCC) between January 2010 and June 2017 were analyzed. The patients were then divided into stage-specific subgroups according to the TNM staging system for comparison. RESULTS: LLR was performed in 153 patients and OLR in 160 patients. LLR is associated with less blood loss (p < 0.001), shorter surgical time (p = 0.001), shorter length of hospital stay (p < 0.001), and lower morbidity rate (p = 0.034). The 5-year overall survival (OS) rates in the LLR group were higher than those in the OLR group (78.1 vs. 57.6%; p = 0.002). Stage-specific subgroup analysis revealed similar 5-year OS in the two groups (stage I: 82.8 vs. 82.6%, p = 0.845; stage II: 80.3 vs. 69.2%, p = 0.638; stage III: 55.6 vs. 34.8%, p = 0.681), as did the 5-year recurrence-free survival. Moreover, the short-term outcomes were better in the LLR group in terms of surgical time, blood loss, and length of hospital stay, and these benefits attenuated with advancing tumor stage. CONCLUSIONS: LLR for HCC is a safe and feasible procedure that does not compromise long-term oncological outcomes. In early tumor stages, LLR might be better in terms of short-term surgical outcomes.

Risk Factors Analysis of Postoperative Pleural Effusion after Liver Resection.

BACKGROUND: Pulmonary complications remain relatively high in morbidities that arise after liver surgery and are associated with increased length of hospital stay and higher cost. Identification of possible risk factors in this retrospective analysis may help reduce operative morbidity and achieve better outcomes. METHODS: In all, 363 consecutive patients underwent elective hepatectomies between July 2008 and November 2013 and these were identified and analyzed retrospectively. Patient demographics and perioperative variables were collected. The main outcome was an analysis of risk factors associated with postoperative pleural effusion (PPE). RESULTS: Of 363 patients receiving hepatectomies, 80 patients (22.0%) developed pulmonary complications. The predominant pulmonary complication in this series is pleural effusion (76 patients, 95%). Univariate analysis found that older age, higher body mass index (BMI), chronic obstructive lung disease, asthma, heart disease, hepatitis C infection, heavy smoking, American Society of Anesthesiology class III and IV, hepatectomy site, combined surgeries, perioperative blood transfusion, and cirrhosis of liver were associated with PPE. Only older age, higher BMI, asthma, heavy smoker, combined gastrointestinal surgeries, and perioperative blood transfusion were identified as independent risk factors in multivariate analysis. CONCLUSION: This study identifies 6 risk factors for PPE. Identification and management of some of these factors could possibly reduce morbidity and improve short-term surgical outcomes.

Outcome Analysis of Patients with Gallstone Disease Receiving Cholecystectomy: A Population-Based Cohort Study.

BACKGROUND/AIMS: Cholecystectomy is generally performed to treat patients with gallstone disease (GSD) in clinical practice. The present study aimed to investigate whether type 2 diabetes mellitus (T2DM) may influence the overall survival of GSD patients. METHODS: The National Health Insurance Research Database, a population-based registry data in Taiwan, was used to identify GSD patients from 2001 to 2008. The risk of cancers and effects of T2DM on the overall survival of GSD patients receiving cholecystectomy were estimated by hazards ratios (HRs) and 95% CIs using the Cox proportional hazard model. RESULTS: Among 392,028 eligible GSD patients, 81,971 underwent cholecystectomy, whereas 310,057 did not. After cholecystectomy, the HR for developing cancer was 1.14. The HR for the overall survival was 0.74-fold lower for patients who underwent cholecystectomy than that for patients who did not. GSD patients without T2DM who underwent cholecystectomy (0.78-fold lower risk) had a longer survival, whereas those with T2DM had shorter survival (1.64-fold higher risk without cholecystectomy and 1.13-fold higher risk with cholecystectomy) compared with those without T2DM who did not undergo cholecystectomy. CONCLUSIONS: Our major findings suggest that T2DM may worsen the prognosis of GSD patients after cholecystectomy, which provides useful insight into the treatment of T2DM among GSD patients in clinical settings.

Maspin mediates the gemcitabine sensitivity of hormone-independent prostate cancer.

Androgen deprivation therapy has constituted the main treatment for prostate cancer; however, tumors ultimately progress to hormone-independent prostate cancer (HIPC), and suitable therapeutic strategies for HIPC are not available. Maspin, which is also known as mammary serine protease inhibitor, has been suggested to be a valuable focus for targeted cancer therapy. Specifically, maspin has been shown to be upregulated after androgen ablation therapy. Gemcitabine is used as a first-line therapy for metastatic castration-resistant prostate cancer, but its disease control rate is low. Furthermore, the role of maspin in the therapeutic efficacy of gemcitabine for HIPC remains unclear. The expression levels of maspin in PC-3 and DU145 cells were determined by real-time PCR and Western blotting. Furthermore, the expression of maspin was silenced using shRNA technology to generate maspin-KD cells. The cytotoxicity of gemcitabine to prostate cancer cells was assessed using 3-[4,5-dimethylthiazol-2-yl]-3,5-diphenyl tetrazolium bromide (MTT) assays, whereas flow cytometry analyses and annexin V-propidium iodide (PI) apoptosis assays were used to assess the ability of gemcitabine to induce apoptosis in maspin-KD and control cells. Additionally, the expression patterns of anti-apoptosis proteins (myeloid cell leukemia 1 (Mcl-1) and B cell lymphoma 2 (Bcl-2)) and pro-apoptosis proteins (Bcl-2-associated death promoter (Bad) and Bcl-2-associated X protein (Bax)) were determined by Western blotting. In this study, PC-3 cells were more resistant to gemcitabine administration than DU145 cells, which correlated with the higher expression levels of maspin observed in PC-3 cells. Furthermore, maspin knockdown enhanced gemcitabine-induced cell death, as evidenced by the increased number of apoptotic cells. Gemcitabine treatment upregulated the levels of anti-apoptosis proteins (Mcl-2 and Bcl-2) in both scrambled control and maspin-KD cells; however, the fold changes in Mcl-1 and Bcl-2 expression were larger in gemcitabine-treated scrambled control cells than in maspin-KD cells. Finally, our findings indicate for the first time that maspin may mediate the therapeutic efficacy of gemcitabine in HIPC. Our results demonstrate that maspin knockdown enhanced the sensitivity of androgen-independent prostate cancer cells to gemcitabine. Therefore, combining gemcitabine with a drug that targets maspin might constitute a valuable strategy for prostate cancer treatment.

Glucose-regulated protein 94 mediates cancer progression via AKT and eNOS in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a crucial health issue worldwide. High glucose-regulated protein 94 (GRP94) expression has been observed in different types of cancer, suggesting a link between tumor progression and GRP94 expression. However, the mechanisms underlying the role of GRP94 in HCC progression remain unclear. We used specific small hairpin RNA (shRNA) to manipulate GRP94 expression in HCC cells. Tissue arrays, MTT assays, xCELLigence assays, and in vivo xenograft model were performed to identify clinicopathological correlations and to analyze cell growth. We found that high GRP94 expression reflected a poor response and a lower survival rate. In vitro and in vivo studies showed that silencing GRP94 suppressed cancer progression. Mechanistically, GRP94 knockdown reduced AKT, phospho-AKT, and eNOS levels but did not influence the AMPK pathway. Our results demonstrated that GRP94 is a key molecule in HCC progression that modulates the AKT pathway and eNOS levels. Our findings suggest that GRP94 may be a new prognostic and therapeutic target for HCC.

E1A-mediated inhibition of HSPA5 suppresses cell migration and invasion in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients. METHODS: The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models. RESULTS: The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model. CONCLUSIONS: The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.

Glucose-regulated protein 78 mediates the anticancer efficacy of shikonin in hormone-refractory prostate cancer cells.

Glucose-regulated protein 78 (GRP78) is a key modulator of prostate cancer progression and therapeutic resistance. Prostate cancer is a worldwide health problem, and therapeutic resistance is a critical obstacle for the treatment of hormone-refractory prostate cancer patients. Shikonin inhibits prostate cancer proliferation and metastasis. However, the role of GRP78 in the cytotoxic effect of shikonin in prostate cancer cells remains unclear. GRP78 expression was abolished using small interfering RNA (siRNA), and the anticancer effects of shikonin were assessed using MTT assays, the XCELLigence biosensor, flow cytometric cell cycle analysis, and Annexin V-PI apoptotic assays. PC-3 cells expressed more GRP78 than DU-145 cells, and the MTT assays revealed that DU-145 cells were more sensitive to shikonin than PC-3 cells. GRP78 knockdown (GRP78KD) PC-3 cells were more sensitive to shikonin treatment than scrambled siRNA control cells. Based on cell cycle analysis and AnnexinV-PI apoptotic assays, apoptosis dramatically increased in GRP78KD cells compared with the control PC-3 in response to shikonin. Finally, in response to shikonin treatment, Mcl-1 and Bcl-2 levels increased in the scrambled control cells treated with shikonin, whereas Bcl-2 decreased and Mcl-1 slightly increased in the GRP78KD PC-3 cells. The levels of Bax and Bad did not change in the scrambled control or GRP78KD cells after shikonin treatment. These results are consistent with the increased sensitivity to shikonin after knockdown of GRP78. GRP78 expression may determine the therapeutic efficacy of shikonin against prostate cancer cells.

Alpha 7-nicotinic acetylcholine receptor mediates the sensitivity of gastric cancer cells to 5-fluorouracil.

Gastric cancer is the second most common cause of cancer mortality worldwide. Most gastric cancer patients are asymptomatic until the advanced stages, for which current therapeutic treatments are suboptimal. 5-Fluorouracil (5-FU), an antimetabolite agent, is widely used in gastric cancer therapy. However, the presence of drug resistance in gastric cancer patients reduces the cytotoxic activity of 5-FU. In gastric cancer, no research has yet been conducted to analyze the effect of alpha 7-nicotinic acetylcholine receptor (A7-nAChR) on the therapeutic response to 5-FU. In this study, we generated A7-nAChR knockdown (A7-nAChR-KD) AGS cells by a small interfering RNA (siRNA) technique in gastric cancer cells. The anti-proliferative effects of 5-FU were determined by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, a terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, and cell cycle determination. We found that A7-nAChR-KD cells were more resistant to 5-FU treatment compared with the scrambled control cells according to the MTT assay. The apoptotic cell population was increased more in scrambled control cells treated with 5-FU than A7-nAChR-KD cells according to the cell cycle distribution and TUNEL assays. We analyzed expression levels of survival and apoptosis-associated proteins (pAkt, Akt, Mcl-1, Bcl-2, Bad, and Bax) altered by 5-FU treatment. Survival and antiapoptosis signaling (pAkt, Akt, Mcl-1 and Bcl-2) was downregulated, and the proapoptotic proteins (Bad and Bax) were upregulated in 5-FU-treated control cells but expression levels of Bcl-2, Bad, and Bad were not altered in 5-FU-treated A7-nAChR-KD cells. This is consistent with A7-nAChR-KD cells exhibiting more resistance to 5-FU treatment. In our study, we carried out an in vitro study on AGS gastric cancer cell line to elucidate the anticancer efficacy and molecular mechanisms of A7-nAChR silencing on 5-FU-induced cell death. The results clearly showed that depletion of A7-nAChR suppressed the drug sensitivity of gastric cancer cells to 5-FU treatment.

Association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer: a meta-analysis.

Several previous studies have investigated the association between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer in various populations. However, these results remain inconsistent. Therefore, we performed this meta-analysis to evaluate the relationship between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer. An extensive literature search was performed to identify all eligible studies regarding this association. The odds ratios (ORs) with 95 % confidence intervals (CIs) were used to estimate the strength of risk under fixed and random effects models. We identified and included eight case-control studies including 2,036 cases and 2,273 controls. No significant association was found between the SULT1A1 Arg213His polymorphism and the risk of bladder cancer under the dominant model; however, those with the SULT1A1 Arg/Arg genotype had a significantly increased risk (OR = 1.218, 95 % CI = 1.067-1.392, P = 0.0044) under the recessive model. In the subgroup analysis of ethnicity, a significant association was observed in Caucasians under the recessive model (OR = 1.269, 95 % CI = 1.069-1.506, P = 0.007). Furthermore, an increased risk of bladder cancer was observed between the Arg213His polymorphism and never smokers in the recessive model (OR = 1.428, 95 % CI = 1.079-1.890, P = 0.013). The results of this meta-analysis indicate that the SULT1A1 Arg213His polymorphism is associated with the risk bladder cancer under a recessive model; however, a possibly higher risk for Caucasians with the Arg/Arg genotype and never smokers needs further investigation.

Combined effects of GSTO1 and SULT1A1 polymorphisms and cigarette smoking on urothelial carcinoma risk in a Taiwanese population.

BACKGROUND/PURPOSE: Cigarette smoking is the main risk factor for urothelial carcinoma of the bladder (UCB). Glutathione S-transferase omega 1 (GSTO1) and sulfotransferase 1A1 (SULT1A1) have been reported to be associated with the metabolism of polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. The aim of the present study was to investigate the combined effects of polymorphisms in GSTO1 and SULT1A1 genes and cigarette smoking on UCB risk in a Taiwanese population. METHODS: A total of 300 patients with histopathologically confirmed UCB and 233 cancer-free controls were recruited from the Department of Urology of Tung's Taichung Metro Harbor Hospital and Taipei Medical University Hospital. A comprehensive interview was conducted to collect personal information, including demographic characteristics and cigarette smoking status. A multivariate-adjusted logistic regression was performed to estimate the risk of UCB. RESULTS: A significantly increased risk of UCB was observed in ever smokers [odds ratio (OR) = 2.3]. The Ala/Ala genotype of the GSTO1 gene and the Arg/Arg genotype of the SULT1A1 gene were associated with a significantly increased risk of UCB, with ORs of 1.8 [95% confidence interval (CI) = 1.2-2.6] and 2.1 (95% CI = 1.6-4.5), respectively. Significantly increased UCB risks were found in heavy smokers with the Ala/Ala genotype of the GSTO1 gene (OR = 4.2) and the Arg/Arg genotype of the SULT1A1 gene (OR = 6.8). Furthermore, a significant synergistic effect in an additive model (OR = 3.5) between the GSTO1 Ala/Ala genotype and the SULT1A1 Arg/Arg genotype on UCB risk was observed. CONCLUSION: The present study provided epidemiological evidence for a significantly increased risk of UCB in ever smokers with the Ala/Ala genotype of the GSTO1 gene and the Arg/Arg genotype of the SULT1A1 gene.

Risk of colorectal cancer in chronic kidney disease: a matched cohort study based on administrative data.

BACKGROUND: The risk of colorectal cancer (CRC) in chronic kidney disease (CKD) patients relative to the general population is unknown. The aim of this population-based study was to investigate the risk of CRC in patients with CKD. METHODS: The study cohort included patients aged ≥18 years diagnosed with CKD between 2004 and 2005 (n = 15,975). The comparison cohort (n = 79,875) included five randomly selected age- and gender-matched controls for each patient in the study cohort. All the subjects were followed up from the date of cohort entry until they developed CRC or until the end of 2006. RESULTS: We identified 15,975 patients with a diagnosis of CKD who matched the inclusion criteria. A total of 460 patients developed CRC during the study period, of whom 116 were from the CKD cohort and 344 were from the comparison cohort. After adjusting for potential confounding factors, the CKD patients not undergoing dialysis were independently associated with a greater risk of CRC (hazard ratio, 1.79; 95% confidence interval [CI] 1.41-2.27). The overall incidence rate of CRC was 341 per 100,000 person-years for CKD patients not undergoing dialysis, compared to 174 per 100,000 person-years. The age-matched hazard ratio of CRC after excluding dialysis patients was 1.64 (95% CI 1.27-2.11) in patients 50 years and older, and 3.7 (95% CI 1.83-7.49) in patients younger than 50 years. CONCLUSIONS: This population-based cohort study indicated that CKD patients not requiring dialysis have an increased risk of CRC compared to the general population, independent of comorbidities.

MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells.

MicroRNAs (miRNAs) play an essential role in regulating gene expression in normal and malignant cells. Expression of the microRNA-200 (miR-200) family has been correlated with malignancy in cancers. However, whether miR-200a/b plays a role in curcumin-mediated treatment of hepatocellular carcinoma (HCC) is unknown. We performed miRNA array analyses in two different HCC cell lines (HepG2 and HepJ5). The expression patterns of miR-200 family members were assessed with real-time PCR. We overexpressed miR-200 family members using a lentiviral system and selected stably transduced clones with antibiotics. The anticancer effects of curcumin on J5-200a, J5-200b, and J5-control cells were assessed by MTT assay, flow cytometry cell cycle analysis, and TUNEL assay. We found that HepG2 cells, which were more resistant to curcumin treatment than HepJ5 cells, expressed higher levels of miR-200a/b. The MTT assay revealed that the overexpression of miR-200a/b in HepJ5 cells conferred enhanced resistance to curcumin treatment compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5-control cells compared with J5-200a and J5-200b cells after curcumin treatment. Finally, we evaluated the levels of Bcl-2, Bax, and Bad, and found a decrease of Bcl-2 levels and increase of Bad levels in the J5-control cells treated with curcumin. The expression levels of miR-200a/b might determine the therapeutic efficacy of curcumin on HCC cells.

Thrombomodulin mediates the progression of epithelial ovarian cancer cells.

Thrombomodulin (TM), a natural anticoagulation factor, maintains circulation homeostasis in endothelial cells. TM has additional roles in modulating inflammation, thrombosis, and carcinogenesis. However, there is little information on the role of TM in the progression and metastasis of ovarian cancer. RNA silencing and cDNA expression vectors were used to manipulate target gene expression in ovarian cancer cells. Cell growth and migration were evaluated by an MTT assay, a wound-healing migration assay, a transwell migration assay, and a biosensor system. In this study, we found that TM silencing may enhance the growth rate of cells. The migratory ability of ovarian cancer cells was enhanced dramatically after TM silencing. TM overexpression in ovarian cells suppressed the proliferation and migration capability. Furthermore, we found that skov-3 cells treated with TM shRNA expressed high levels of fibronectin and vimentin and that the expression of these markers correlated positively with their migratory ability. Our results demonstrate that TM expression may regulate cell growth and migration in ovarian cancer cells. This finding suggests that TM may be a novel prognostic and therapeutic target for ovarian cancer.

Intersphincteric resection for very low rectal cancer: clinical outcomes of open versus laparoscopic approach and multidimensional analysis of the learning curve for laparoscopic surgery.

BACKGROUND: Laparoscopic rectal cancer surgery is regarded as more complex because of its technical difficulties in pelvic exposure, dissection, and sphincter preservation. This study therefore aimed to investigate the feasibility of laparoscopic resection for low rectal cancer using intersphincteric resection (ISR) and to assess its short-term oncological outcomes. Further, we intended to analyze the learning curve for laparoscopic surgery and identify the factors influencing the learning curve. METHODS: Patients with low rectal cancer who received open or laparoscopic ISR were retrospectively chart reviewed. The surgical and oncological outcomes were evaluated. Comparisons of operating time, estimated blood loss, surgical outcomes, and histopathologic status were analyzed. Also, operating time was used as a technical indicator for learning curve analysis. RESULTS: The mean estimated blood loss was 265 mL (range, 100-800 mL) in the open group and 104 mL (range, 30-250 mL) in the laparoscopic group. There was a significant difference between these two groups (P < 0.001). Operative experience analysis showed that the mean operating time was 402.1 min (range, 210-570 min) in the first stage and 331.4 min (range, 210-450 min) in the second stage, and on pathologic examination the mean number of lymph nodes harvested was 11.1 (range, 5-21) in the first stage and 18.3 (range, 11-31) in the second stage, with statistical differences between these two stages (P = 0.034 and P = 0.004, respectively). Multifactorial analysis showed that operating time was associated with surgeons' experience (<18 or ≥18 cases) (odds ratio = 2.918, 95% CI 1.078-7.902). Protective stoma creation was also associated with surgeons' experience (odds ratio = 3.999, 95% CI 1.153-13.86). CONCLUSIONS: Our data show that laparoscopic ISR for low rectal cancer is feasible and safe. Surgeons' experience improved operating time and postoperative complications.

Robotic versus laparoscopic hepatectomy: A single-center, propensity score- matched study.

BACKGROUND: Although the effectiveness of robotic hepatectomy (RH) has been evaluated in several studies, the superiority of RH over other approaches has not been definitely established. Therefore, in the present propensity score-matched cohort study, we compared RH and laparoscopic hepatectomy (LH) in terms of perioperative and oncologic outcomes. METHODS: This retrospective study included patients who underwent RH or LH for benign and malignant liver lesions at a single center in Taiwan at any time between 2014 and 2020. Confounding factors, specifically age, sex, body mass index, American Society of Anesthesiologists score, IWATE criteria, and Charlson comorbidity index, were adjusted through propensity score matching (PSM). RESULTS: A total of 329 patients were finally included in this study. Two homogeneous groups (RH and LH; n, 72 each) were formed using PSM. The RH group had a longer operative time (median: 231 vs.180 min, respectively; P = .001) and lower conversion (to open surgery) rate (9.7% vs.0.0%, respectively; P = .013) than did the LH group. However, the two groups did not differ in terms of other perioperative outcomes, specifically blood loss, hospital stay, intensive care unit admission, mortality, morbidity, or tumor margin status. CONCLUSIONS: The rate of conversion to open surgery is lower in RH than in LH. Although operative time is longer in RH than in LH, RH is feasible and safe for patients with benign or malignant liver lesion. Our study also demonstrated comparable oncological results in patients with hepatocellular carcinoma between LH and RH group.

Prediction of 5-Year Weight Loss and Weight Regain According to Early Weight Loss after Sleeve Gastrectomy.

BACKGROUND: Patients with morbid obesity exhibit sustained weight loss after sleeve gastrectomy (SG), but some individuals exhibit subsequent weight regain in the following years. Early weight loss was proven as a predictor of short- and mid-term weight loss and regain. However, the long-term effects of early weight loss have yet to be fully investigated. This study investigated the predictive effects of early weight loss on long-term weight loss and regain after SG. METHODS: Data of patients who underwent SG from November 2011 to July 2016 and followed through July 2021 were collected retrospectively. Weight regain was defined by weight increase more than 25% of their lost weight at the first postoperative year. Linear regression analysis and Cox proportional hazards analysis were performed to evaluate the correlations among early weight loss, weight loss, and weight regain. RESULTS: Data of 408 patients were included. The percentages of total weight loss (%TWL) at postoperative months 1, 3, 12, and 60 were 10.6%, 18.1%, 29.3%, and 26.6%, respectively. The %TWL at months 1 and 3 were significantly correlated with %TWL after 5 years (P < .01). The weight regain rate was 29.8% at 5 years. The %TWL at months 1 and 3 significantly influenced weight regain (hazard ratio: 0.87 and 0.89, P = .017 and .008). CONCLUSION: Early weight loss may be used to predict weight loss and regain 5 years after SG. Patients with poor early weight loss are recommended to receive early interventions to achieve long-term weight loss and prevent weight regain.