Chemoprotective effect of boeravinone B against 1,2-dimethyl hydrazine induced colorectal cancer in rats via suppression of oxidative stress and inflammatory reaction.

Background: Colorectal cancer (CRC) has few or no symptoms and is often diagnosed at its end stage. Boeravinone B (BB) is a natural rotenoid which induces an antioxidative effect and has been used in cancer prevention. In this study, we scrutinized the chemoprotective effect of BB against 1,2dimethyl hydrazine (DMH) induced CRC in rats. Methods: Subcutaneous administration of DMH (40 mg/kg) was used for the induction of CRC in rats, followed by oral administration of BB. The body weight, tumor volume, tumor incidence, and total number of tumors were estimated in all rat groups rats except the normal group. Antioxidant parameters, phase I and II enzymes, and inflammatory cytokines and parameters were estimated at the completion of the study. Results: DMH induced group rats exhibited a tumor incidence of 100% along with several tumors/polyps per tumor­bearing rat, while BB treatment remarkably suppressed the incidence of tumors and suppressed polyps per tumor bearing rat. BB treatment significantly (P<0.001) altered the level of antioxidant parameters, phase I and phase II enzymes, and cytokines such as TNF-α, IL-1ß, IL-4, IL-6, and IL-10, and treatment significantly (P<0.001) suppressed the level of inflammatory cytokines, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and inducible nitric oxide synthase (iNOS). Conclusions: BB treatment considerably suppresses colon cancer via its antioxidant and anti-inflammatory mechanism.

Circ_0081143 Contributes to Gastric Cancer Malignant Development and Doxorubicin Resistance by Elevating the Expression of YES1 by Targeting mziR-129-2-3p.

Background/Aims: The increased mortality of gastric cancer (GC) is mainly attributed to the development of chemoresistance. Circular RNAs, as the novel type of biomarkers in GC, have attracted wide attention. The purpose of this study was to investigate the functional role of circ_0081143 in GC with doxorubicin (DR) resistance and its potential action mechanism. Methods: The expression of circ_0081143, miR-129-2-3p and YES proto-oncogene 1 (YES1) in GC tissues and cells was measured by quantitative real-time polymerase chain reaction. The half maximal inhibitory concentration value was calculated based on the MTT cell viability assay. Cell proliferation and apoptosis were monitored by MTT and flow cytometry assays. Transwell assays were employed to check cell migration and invasion. The protein levels of YES1 and apoptosis-related proteins were detected by western blotting. The interaction between miR-129-2-3p and circ_0081143 or YES1 was verified by dual-luciferase reporter and pull-down assays. A tumorigenicity assay was conducted to verify the role of circ_0081143 in vivo. Results: Circ_0081143 was highly expressed in DR-resistant GC tumor tissues and cells. Depletion of circ_0081143 reduced DR resistance and inhibited DR-resistant GC cell proliferation, migration and invasion. Circ_0081143 targeted miR-129-2-3p and inhibited the role of miR-129-2-3p. In addition, YES1 was a target of miR-129-2-3p, and its function was suppressed by miR-129-2-3p. Importantly, circ_0081143 positively modulated the expression of YES1 through mediating miR-129-2-3p. Circ_0081143 knockdown weakened the DR-resistant GC tumor growth in vivo. Conclusions: Circ_0081143 knockdown weakened DR resistance and blocked the development of DR-resistant GC by regulating the miR-129-2-3p/YES1 axis. Our data suggest that circ_0081143 is a promising target for the treatment of GC with DR resistance.

Prognostic Significance of Preoperative Lymphocyte-to-C-Reactive Protein Ratio in Patients with Non-Metastatic Colorectal Cancer.

BACKGROUND: The inflammatory indexes are attracting increasing attention as a prognostic predictor for colorectal cancer (CRC). However, the prognostic value of the preoperative lymphocyte-to-C-reactive protein ratio (LCR) in patients with non-metastatic CRC remains to be established. METHODS: A total of 955 patients from 2010 to 2014 at a single center were included. Receiver operating characteristic curves (ROC) were generated to define the optimal cutoff value of the inflammatory indexes, and the areas under the curve (AUC) were calculated to compare the predictive value among the inflammatory indexes. The Fine and Gray competing risk regression model and Cox proportional hazard model were used to determine the prognostic factors for cancer-specific survival (CSS) and overall survival (OS) by using sub-distribution hazard ratio (SHR) and hazard ratio (HR) as size effects, respectively. RESULTS: A ratio of 6500 was defined as the optimal cutoff value for LCR for dividing CRC patients into the high (> 6500, n = 528) and low (≤ 6500, n = 427) LCR groups. The LCR had the highest value of prognostic prediction among all inflammation-based scores. Low LCR was significant correlated with several clinicopathological features of tumor invasion and development. The patients with low LCR had poorer CSS and OS as compared to those with high LCR. Multivariate analyses showed that low LCR was independently associated with worse OS (HR = 0.61, 95% CI: 0.53-0.70) and CSS (SHR = 0.55, 95% CI: 0.43-0.71). CONCLUSION: Preoperative LCR can be a useful biomarker for prognostic prediction in non-metastatic CRC patients with a better predictive value than other inflammatory indexes.

Clinical study of XiangShaLiuJunZi decoction combined with S-1 as maintenance therapy for stage III or IV gastric carcinoma and colorectal carcinoma.

INTRODUCTION: S-1, a new oral fluorouracil chemotherapeutical drug, has been increasingly used in clinical maintenance after first-line chemotherapy for stage III or IV gastric carcinoma (GC) and colorectal carcinoma (CRC) for its own advantages. XiangshaLiujunzi Decoction (XSLJZD), a classic traditional Chinese medicine (TCM) formula with effects of alleviating the adverse reactions of chemotherapy and improving the quality of life of cancer patients has been gradually confirmed, with no more reports about the maintenance therapy mode of combination of chemotherapeutic drugs and TCM. We designed the study of XSLJZD combined with S-1 in the maintenance therapy of Stage III or IV GC and CRC, and hoped that this research program will go further and comprehensively evaluate its efficacy and safety. OBJECTIVES: The aim of this study was to determine the efficacy and safety of XSLJZD combined with S-1 in the maintenance therapy of stage III or IV GC and CRC. METHODS: This study is an open, single-center, randomized study. Patients with stage III or stage IV GC and CRC will be randomized (1:1) into S-1group, S-1 combined with XSLJZD group for 5 years of maintenance therapy. The primary endpoint was progression-free survival, and secondary end point was overall survival and Quality of Life Assessment (QOLA), which include an improvement in symptoms before and after treatment, Karnofsky Performance Status, and adverse events assessment. DISCUSSION: This study will provide meaningful clinical information about the combination of chemotherapeutic drugs S-1 with TCM in the maintenance therapy of stage III or IV GC and CRC. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16008575.

Primary gastric melanoma in a young woman: A case report.

BACKGROUND: Most melanomas identified in the stomach are metastatic. The primary gastric melanoma (PGM) is extremely rare. As such, clinical reports of PGM are scarce in the literature, lending to the challenge of diagnosis and treatment. CASE SUMMARY: A 31-year-old woman presented with a 1-mo history of dysphagia but no symptoms of abdominal pain, abdominal distension, nausea, vomiting, hematemesis, or melena. The patient reported an unintentional weight loss of 6 kg within that time. History-taking revealed no previous medical conditions or surgical events. Abdominal computed tomography at a local hospital had suggested gastric tumor. Endoscopic examination in our hospital found a large, irregular, black mass. Subsequent laparoscopic exploration found the tumor on the side of the stomach fundus penetrating through the serosa, and enlarged lymph nodes (groups 1, 3, 7, and 9) fused into a mass, surrounding the peripheral artery and inseparable. Postoperative immunohistochemistry suggested gastric malignant melanoma. Positron emission tomography-computed tomography confirmed PGM. Treatment with programmed cell death protein 1 antagonist (toripalimab) plus chemotherapy (paclitaxel) was initiated but discontinued upon tumor bleeding. At the last telephone follow-up, the patient reported poor general condition but was alive. CONCLUSION: Although unresolved and ongoing, this rare case of PGM expands the overall knowledge about this rare tumor's diagnosis and management.

Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma.

Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P=0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coefficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC.

[Association of early diarrhea and fecal volume with anastomotic leakage after low anterior resection of rectal cancer].

OBJECTIVE: To evaluate the association of early diarrhea and fecal volume with anastomotic leakage after low anterior resection (LAR) of rectal cancer. METHODS: Clinical data of 541 patients with rectal cancer undergoing LAR at The Affiliated Hospital of Guangdong Medical College between January 2007 and January 2017 were analyzed retrospectively. Early postoperative diarrhea was defined as at least one occurrence of more than 50 ml watery stool or at least four times defecation per day within 7 days after surgery. The volume of fecal discharge from the transanal drain was measured at daily intervals for 3 days after surgery. Association of early diarrhea and anastomotic leakage was analyzed using logistic regression model. The accuracy of fecal volume in predicting anastomotic leakage was evaluated using receiver operating characteristics (ROC) curve. RESULTS: There were 319 males and 222 females with mean age of 59.3 years. Early postoperative diarrhea occurred in 99(18.3%) patients, and 41(7.6%) patients developed anastomotic leakage. The incidence of anastomodc leakage in patients with early diarrhea was significantly higher as compared to those without early diarrhea (15.2% vs. 5.9%, P=0.000). Multivariate analysis revealed that early diarrhea (OR=33.940, 95%CI: 8.423 to 89.240) and the distance between the tumor and the anal verge less than 7 cm (OR=13.085, 95%CI: 2.117 to 44.556) were independent risk factors for anastomotic leakage, while the presence of a transanal tube was an independent protective factor (OR=0.474, 95%CI: 0.122 to 0.881). The total fecal volume for 3 days after surgery was calculated in 162 patients with a transanal tube. The median fecal volume was 210 (100 to 4360) ml and 60 (0 to 480) ml in patients with and without anastomotic leakage respectively(P=0.000). ROC curve showed that the cut-off value of fecal volume for anastomotic leakage was 110 ml and the area under the curve was 0.824 with a high sensitivity of 85.7% and specificity of 81.3%. CONCLUSIONS: Early postoperative diarrhea after LAR procedure of rectal cancer may be an early predictor of anastomotic leakage, and fecal volume for 3 days after surgery ≥110 ml can accurately predict anastomotic leakage. Active prevention and management of early postoperative diarrhea may reduce the risk of anastomotic leakage.

Primary Pulmonary Paraganglioma: A Case Report and Review of Literature.

Primary pulmonary paraganglioma is a rare disease. We report a case of a 37-year old female patient with space-occupying lesions in the right lower pulmonary lobe during a routine examination without any symptoms. The patient underwent video-assisted thoracoscopic surgery (VATS) resection of the right middle lobe and dissection of hilar and mediastinal lymph nodes under general anesthesia. She recovered without recrudescence. Preoperative diagnosis is difficult. Accurate diagnosis requires pathological examination, and immunohistochemical test is particularly important. Complete resection is the first treatment option for solitary primary pulmonary paraganglioma; however, VATS is a better technique. Given the high local control rates and few complications of radiotherapy, it is considered as a standard treatment.

Laparoscopic resection of primary adrenal ganglioneuroma: A case report and review of the literature.

Adrenal ganglioneuroma (AGN) is an extremely rare, benign tumor that originates from the neural crest tissue of the sympathetic nervous system. The majority of cases are detected incidentally, since the disease often lacks clear clinical manifestations or is asymptomatic. In addition, AGN is often misdiagnosed as being an adrenal adenoma or adrenal pheochromocytoma. The present study describes a 58-year-old female who visited the outpatient clinic of the Affiliated Hospital of Guangdong Medical College (Zhanjiang, Guangdong, China) with symptoms of face and lower extremity dropsy. Color Doppler ultrasonography revealed a solid tumor in the right kidney, and abdominal computed tomography identified an irregular, solid tumor measuring ~6×4.5×7 cm3 and arising from the right adrenal gland, with a clear boundary. Magnetic resonance imaging was not performed. An initial diagnosis of adrenal adenoma was established. The patient was treated by laparoscopy in order to remove the tumor. However, following surgery, a pathological examination suggested that the tumor was a GN originating from the adrenal medulla. The formation of a correct diagnosis can be extremely challenging, as AGNs do not exhibit any specific clinical manifestations. Therefore, detection often depends entirely upon imaging studies, and the final diagnosis can be only by confirmed following a histopathological evaluation.

Surgical resection and post-operative radiotherapy in an adult renal neuroblastoma patient with multiple bone and joint metastases: A case report.

Renal neuroblastoma is uncommon, particularly in adults, with only a few cases having been reported in studies published in the English language. The incidence is only 0.12 cases/1 million individuals in those aged >20 years. Studies of the pathogenesis, biological characteristics, treatment and prognosis of renal neuroblastoma are limited due to this low incidence. The present study reports the case of a 22-year-old adult female who was diagnosed with a left renal neuroblastoma by computed tomography (CT), bone scan and pathological examination. The patient underwent a left nephroureterectomy, ipsilateral lymph node dissection and post-operative radiotherapy, prior to discharge 60 days after admittance. At the nine-month follow-up examination, the patient showed no evidence of recurrence, progression or metastatic disease on the CT scans of the chest, abdomen and pelvis. Renal neuroblastoma is extremely uncommon in adults. The diagnosis and treatment of renal neuroblastoma is complicated by the overall low incidence, lack of specific treatment guidelines, advanced disease state due to late presentation, and its associated co-morbidities. Further study of the pathogenesis, biological and clinical characteristics, and treatment of renal neuroblastoma is required to provide an optimal treatment for patients and to improve the patient's quality of life.

Small cell carcinoma of the urinary bladder: A case report and review of the literature.

Small cell carcinoma of the urinary bladder (SCBC) is a type of rare malignant tumor of the urinary tract. As it does not have specific symptoms and its epidemiological features are similar to transitional cell carcinoma of the bladder, it is often misdiagnosed. SCBC is highly aggressive, metastasizes very early and has a poor prognosis, and consequently, it has become a focus for urological surgeons and oncologists. An 82-year-old male visited the Department of Urinary Surgery, in the Affiliated Hospital of Guangdong Medical College (Zhanjiang, China), due to gross hematuria that had persisted for one week. Abdominal computed tomography showed a neoplasm of ~6×6×7 cm on the anterior wall of the bladder. The initial diagnosis was of uroepithelial cell carcinoma of the bladder and surgery was performed to remove the tumor. However, the subsequent pathological examination suggested that the tumor was an SCBC. Small cell carcinoma is a highly malignant disease, with a high mortality rate, and it rarely occurs in the bladder. Upon review of a large number of studies, SCBC was not found to present with specific symptoms, making the early diagnosis of the disease difficult, however, commonly occurring symptoms included dysuria, painless gross hematuria and urinary tract obstruction.

Effect of stable transfection with PHD3 on growth and proliferation of HepG2 cells in vitro and in vivo.

OBJECTIVE: To establish a human hepatoma HepG2 cell line with stable expression of Prolyl hydroxylase domain 3 (PHD3) gene and study its effect of growth and proliferation in nude mice xenograft tumor. METHODS: Eukaryotic expression vectors of pcDNA 3.1-PHD3 was constructed. HepG2 cells were transfected with recombinant plasmid pcDNA 3.1-PHD3 and empty vector plasmid pcDNA 3.1 by lipofectamine 2000 as transfected group, control group respectively, while the HepG2 cell without any operation was considered as parental group. Steady expression cells were gotten by G418 selecting. RT-PCR and agarose gel electrophoresis were used to confirm the expression of PHD3 in HepG2 cells and transfection successfully. The growth of these cells in vivo were also observed by injecting three groups of cell into nude mice, and volume were measured and compared. RESULTS: The recombinant plasmid pcDNA 3.1-PHD3 and empty vector plasmid pcDNA 3.1 were successfully transfected into human hepatoma HepG2 cell line and showed stable expression in this cell line. Tumors were observed in nude mice when the transfectant cells were xenografted successfully, The average tumor size of PCDNA (3.1)-PHD3 groups are significant different compared with other two groups (P < 0.001). CONCLUSION: The PHD3 gene may have negative influence of growth and proliferation on HepG2 cells in vitro. The PHD3 may be a potentially tumor suppressor.

Tumor suppressor TSLC1 inhibits growth, proliferation, invasiveness and angiogenesis in nude mice xenografted tumor of Eca109 cells.

Tumor suppressor in lung cancer 1 (TSLC1) is a novel tumor suppressor gene whose inactivation is implicated in the occurrence, invasion, metastasis and prognosis of esophageal cancer. TSLC1 was studied by comparing the tumor formation of TSLC1 transfectant and control cells in nude mice. Compared with blank group and mock group, tumor size and infiltrating range of transfected group was less, differentiation of tumor tissue was slightly better, and differences of tumor angiogenesis was worse. There was no obvious difference between blank group and mock group. We have shown TSLC1 gene inhibited the growth proliferation, infiltration and angiogenesis of Eca109 cells.

Function and expression of prolyl hydroxylase 3 in cancers.

Hypoxia inducible factor (HIF) is a product of tumor cells that plays an important role in protecting tumor cells and adjusting to low oxygen tension through driving the progression and aggressiveness of tumors and changing the growth, angiogenesis, differentiation and metastasis of tumors. Prolyl hydroxylase 3 (PHD3) is a member of PHDs that are induced in hypoxia. Many studies have shown that PHD3 not only can hydroxylate HIF-1α, but also has various other biological functions. Thus PHD3 plays significant roles in suppressing the growth, angiogenesis, differentiation and metastasis of tumors and promoting apoptosis of tumors under hypoxic conditions. It may become a new tumor suppressor gene and also may become a new approach to investigate tumors.

Construction of a recombinant eukaryotic expression vector containing PHD3 gene and its expression in HepG2 cells.

Prolyl hydroxylase domain 3 (PHD3) is a hypoxia inducible factor-α (HIFα) regulator; it degrades HIFα in the presence of oxygen. Recently, there have been an increasing number of studies about the role of PHD3 in proliferation and apoptosis of cancer cells. However, most of the evidence for the role of PHD3 is observational, and little is known of the molecular mechanism. In our current study, we constructed a recombinant eukaryotic expression vector containing the PHD3 gene and detected its biological activity in human hepatoma cell line (HepG2 cells). We successfully constructed a recombinant pcDNA 3.1(+)-PHD3 plasmid; the results showed that PHD3 overexpression could inhibit the proliferation of HepG2 cells and induce apoptosis by activating caspase-3 activity. Our study has provided preliminary materials and data for further investigation of the effect of PHD3 on HepG2 cells.