Hyperprogression under treatment with immune-checkpoint inhibitors in patients with gastrointestinal cancer: A natural process of advanced tumor progression?

Immunotherapy has shown great promise in treating various types of malignant tumors. However, some patients with gastrointestinal cancer have been known to experience rapid disease progression after treatment, a situation referred to as hyperprogressive disease (HPD). This minireview focuses on the definitions and potential mechanisms of HPD, natural disease progression in gastrointestinal malignancies, and tumor immunological microenvironment.

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX).

BACKGROUND: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers. METHODS: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis. RESULTS: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. CONCLUSION: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02).

PURPOSE: As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy. PATIENTS AND METHODS: In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). RESULTS: Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1- patients, respectively (P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% (P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab. CONCLUSION: The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.

Lysyl oxidase and hypoxia-inducible factor 1α: biomarkers of gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression. AIM: To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α (HIF1α) are prognostic and predictive biomarkers in GC. METHODS: A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC. RESULTS: Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases , deeper infiltration depth and later tumor-node-metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC. CONCLUSION: LOX and HIF1α can be used as prognostic and predictive biomarkers for GC.

Overexpression of c-kit(CD117), relevant with microvessel density, is an independent survival prognostic factor for patients with HBV-related hepatocellular carcinoma.

BACKGROUND: To explore new biomarkers for indicating the recurrence and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after tumor resection, we investigated the expression and prognostic value of c-kit(CD117) in HBV-related HCC. MATERIALS AND METHODS: Immunohistochemistry was used to estimate the expression of c-kit(CD117) and CD34 in the liver cancer tissues. The correlations between the expression of these biomarkers and the clinicopathologic characteristics were analyzed. RESULTS: The positive rate of c-kit(CD117) expression in 206 HCC cases was 48.1%, and c-kit expression was significantly related with CD34-positive microvessel density. CD34-microvessel density numbers were much higher in c-kit(+) HCC tissues than in c-kit(-) HCC tissues (44.13±17.01 vs 26.87±13.16, P=0.003). The expression of c-kit was significantly higher in patients with Edmondson grade III-IV (P<0.001) and TNM stage III (P<0.001). Moreover, Kaplan-Meier survival analysis showed that c-kit (P<0.001) expression was correlated with reduced disease-free survival (DFS). Multivariate analysis identified c-kit as an independent poor prognostic factor of DFS in HCC patients (P<0.001). CONCLUSION: Increased c-kit expression could be considered as an independent unfavorable prognostic factor for predicting DFS in HBV-related HCC patients after surgery. These results could be used to identify patients at a higher risk of early tumor recurrence and poor prognosis.

KRAS mutation and primary tumor location do not affect efficacy of bevacizumab-containing chemotherapy in stagae IV colorectal cancer patients.

This study aims to investigate the efficacy of bevacizumab-combined chemotherapy (BCC) in Chinese stage IV colorectal cancer (CRC), and analyze the relationship between clinicopathological features with survival. Patients with stage IV CRC treated with BCC were analyzed retrospectively. 217 metastatic CRC (mCRC) patients were collected, out of which79 were right-sided CRCs and 138 were left-sided ones. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤2, single agent chemotherapy, poor/mucous/signet ring cell component, second-and further-line of bevacizumab administration, multiple metastasis sites had comparatively worse survival. Among 141 patients with known KRAS status, 55 patients harbored KRAS mutation and 86 had wild type KRAS. The ORR and DCR were 41.9% and 78.9%, respectively, in patients with wild type KRAS, while ORR and DCR was 38.7% and 77.9%, respectively, in patients with KRAS mutation. The median PFS of patients with wild type and mutant KRAS were 8.38, and9.59 months, respectively; whereas the OS was 23.00 and 21.26 months, respectively for mCRC patients with wild-type and mutant KRAS. Cumulatively, our study indicated that BCC was effective and beneficial for Chinese stage IV CRC patients. KRAS mutation status and tumor location were not a prognostic factor for survival.

Leucine-rich alpha-2-glycoprotein-1, relevant with microvessel density, is an independent survival prognostic factor for stage III colorectal cancer patients: a retrospective analysis.

BACKGROUND: Leucine-rich alpha-2-glycoprotein-1 (encoded by LRG1) has been shown to be involved in multiple cancer progression and angiogenesis. LRG1 has been shown to be one of the five plasma proteins that can be used for colorectal cancer (CRC) diagnosis. The objective of the current study was to explore relationship between LRG1 protein expression and microvessel density (MVD) in stage III CRC. METHODS: A single-center retrospective analysis of all stage III CRC who underwent surgery and adjuvant chemotherapy was carried out. LRG1 and CD34 were tested in tumor tissues by immunohistochemistry (IHC). RESULTS: LRG1 protein expression was significantly associated with MVD (P <0.001) and other clinicopathological parameters, including T stage (P=0.028), differentiation (P=0.035) and vascular invasion (P=0.007). Cox multivariate regression analysis showed that LRG1 protein expression was an independent poor predictive factor for both disease-free and overall survival. CONCLUSION: LRG1 protein expression can be used as a prognostic marker for stage III CRC along with its use as a diagnostic marker for CRC in general.

Timing of chemotherapy-induced neutropenia: the prognostic factor in advanced pancreatic cancer patients treated with gemcitabine / gemcitabine-based chemotherapy.

Chemotherapy-induced neutropenia (CIN) was reported to be a predictor of better survival in several cancers. The objective of our study is to evaluate the relationship between the timing (onset) of CIN and prognosis. Between June 2008 and June 2015, 134 patients with confirmed advanced pancreatic cancer received at least one cycle of gemcitabine / gemcitabine-based chemotherapy as first-line chemotherapy were eligible for assessment. Timing of CIN was categorized into early onset and non-early onset CIN group. The end of cycle 2 was the cutoff to differentiate early onset or non-early onset. The correlation between timing of CIN with survival was analyzed by Kaplan-Meier method and Cox proportional hazards model. Median overall survival (OS) was 8.05 months (95% CI: 5.97-10.13) for patients with early onset CIN compared with 5.82 months (95% CI: 5.00-6.63) for patients without early-onset neutropenia (P = 0.022). Multivariate analysis proved that timing of CIN was an independent prognostic factor, hazard ratios of death was 0.696 (95% CI: 0.466-0.938) for patients with early onset CIN. In conclusion, timing of CIN is an independent predictor of prognosis in patients with advanced pancreatic cancer undergoing gemcitabine / gemcitabine based chemotherapy. Early-onset CIN predicts better survival.

Decreased spinal endomorphin-2 contributes to mechanical allodynia in streptozotocin-induced diabetic rats.

Diabetic neuropathic pain (DNP) plays a major role in decreased life quality of diabetes patients, however, the neural mechanisms underlying DNP remain unclear. Endomorphins are the endogenous ligands for mu-opioid receptor. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, using a streptozotocin induced diabetic rat model that displayed obvious mechanical allodynia, it was found that the expression of spinal EM2 was significantly decreased in DNP rats. While intrathecal administration of exogenous EM2 attenuated mechanical allodynia in DNP rats, the mu-opioid receptor antagonist ß-funaltrexamine facilitated these events. It was found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of diabetes-induced oxidative stress. Taken together, our results provide the first evidence that the reduction in the level of an endogenous opioid in primary afferents was significantly associated with DNP. This indicates that the chronic pain associated with DNP might be due to the loss of an inhibitory effect on pain signal transmission.

Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study.

BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

[Prognostic Factors of Stage 3 Colorectal Cancer in 433 Patients].

OBJECTIVE: To summarize the prognostic factors of stage 3 colorectal cancer. METHODS: The clinical data of 433 patients with stage 3 colorectal cancer who were admitted to our hospital from January 2005 to December 2008 for radical surgery and adjuvant chemotherapy were retrospectively analyzed. Relationship of their clinicopathologic features and treatment with the prognosis were analyzed. RESULTS: Of these 433 stage 3 patients,the mean disease-free survival was (72.37 ± 2.11) months and mean overall survival was (79.91 ± 2.02) months; however, the median survival times were not reached. The 1-,3-, and 5-year disease-free survival rate were 86.8%,77.9%, and 57.0% and the overall survival rate were 91.5%,75.1%, and 63.3%. Multivariate COX regression analysis displayed that intestine obstruction before surgery, complications after surgery,tumor location,positive surgical margin, neural cell infiltration,vessel cancer embolus, TNM stage, lymph node ratio, adjuvant chemotherapy regimens, and chemotherapy duration were the independent factors affecting disease-free and overall survivals in patients with stage 3 colorectal cancer. The efficacies of FOLFOX and XELOX regimens were significantly correlated with patient's age, complications,tumor location,and chemotherapy duration. CONCLUSIONS: Complications,tumor location, TNM stage, and positive surgical margin are the independent prognostic factors of stage 3 colorectal cancer. FOLFOX and XELOX regimen can remarkably improve prognosis,and a longer duration of chemotherapy can achieve better survival.

Antinociceptive effects of endomorphin-2: suppression of substance P release in the inflammatory pain model rat.

Endomorphin-2 (EM2) and Substance P (SP) exert suppressive and facilitative influences upon nociception, respectively. Although EM2 and SP were often co-expressed in single neurons in dorsal root ganglion (DRG), it is still unknown if and how the nociception-suppressive influences of EM2 might be exerted upon nociception-facilitative effects of SP in the DRG neurons. We examined these issues in the inflammatory pain model rats produced by subcutaneous injection of the complete Freund's adjuvant into the hind paw. The paw withdrawal threshold for mechanical allodynia was measured. Changes of EM2 and SP release were estimated by measuring intrathecal levels of EM2 and SP through in vivo microdialysis analysis of cerebrospinal fluid. The mechanical allodynia was dose-dependently attenuated by intrathecal injection of EM2 or a neurokinin-1 receptor antagonist, and facilitated by intrathecal injection of SP or a mu-opioid receptor (MOR) antagonist. Importantly, intrathecal level of SP was found to be lowered by intrathecal injection of EM2. Morphologically, colocalization of EM2-, MOR- and SP-immunoreactivity in single DRG neurons was observed by immunofluorescent histochemistry, and co-expression of EM2 and SP in large, dense-cored presynaptic vesicles in primary afferents, as well as localization of MOR on pre- and postsynaptic membrane in spinal dorsal horn, was also confirmed electron miscroscopically. Thus, the results indicated that analgesic influences of EM2 upon inflammatory pain might be exerted through suppression of SP release, supporting the assumptions that binding of EM2 to presynaptic MOR might induce such effects.

Nanoparticle albumin-bound paclitaxel combined with cisplatin as the first-line treatment for metastatic esophageal squamous cell carcinoma.

Esophageal cancer is a major health hazard in many parts of the world and is often diagnosed late. The objective of this study was to explore the efficacy and safety of nanoparticle albumin-bound paclitaxel (Nab-PTX) combined with cisplatin (DDP) in patients with metastatic esophageal squamous cell carcinoma (ESCC). Patients with histologically confirmed ESCC were treated with Nab-PTX 250 mg/m(2) and DDP 75 mg/m(2) intravenously on day 1, every 21 days. Evaluation was performed after every two cycles of therapy and the therapy was continued until disease progression or unacceptable toxicity. From April 2010 to December 2012, 33 patients were enrolled. Ten patients had recurrent and metastatic tumors after surgery and 23 patients were diagnosed with unresectable metastatic disease. Patients received a median of four cycles of therapy (ranging from two to six cycles). Twenty patients achieved partial response and nine patients achieved stable disease; no complete response was observed. The objective response rate was 60.6% and the disease control rate was 87.9%. The median progression-free survival was 6.2 months (95% confidence interval: 4.0 to 8.4 months) and the median overall survival was 15.5 months (95% CI: 7.6 to 23.4 months). Only four patients experienced grade 3 adverse events, including vomiting, neutropenia, and sensory neuropathy. The most common adverse events were nausea/vomiting (81.8%), neutropenia (63.6%), leucopenia (48.5%), anemia (24.2%) and sensory neuropathy (24.2%). In conclusion, the combination of Nab-PTX and DDP is a highly effective and well-tolerated first-line treatment in metastatic ESCC.

Sorafenib combined with TACE in advanced primary hepatocellular carcinoma.

BACKGROUND/AIMS: To evaluate the effectiveness and safety of sorafenib combined with transarterial chemoembolization (TACE) in patients with advanced primary hepatocellular carcinoma. METHODOLOGY: A retrospective analysis of 65 patients with advanced primary hepatocellular carcinoma who had been administered sorafenib for more than one month and treated by TACE was performed. The tumor response was evaluated according to the response evaluation criteria in solid tumors and any side effects were recorded. RESULTS: Twelve patients entered a partial remission, 42 entered a stable condition, and the disease progressed in 11 patients. The disease control and objective regression rates were 83.1% and 18.5%, respectively. The one-year survival rate was 63.1%. Among the cases, the median overall survival time was 17 months, and the median time to progression was 9 months. The overall side effects rate was 78.5% and most were relieved after treatment. CONCLUSIONS: Sorafenib combined with TACE is a safe and effective treatment of advanced primary hepatocellular carcinoma.

Molecular biology and clinical features of hereditary non-polyposis colorectal cancer.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly inherited disease associated with germ-line mutations in mismatch repair genes and microsatellite instability. This article reviews the molecular biology and clinical pathology of HNPCC.

Trastuzumab combined with docetaxel-based regimens in previously treated metastatic gastric cancer patients with HER2 over-expression.

BACKGROUND/AIMS: This study evaluates the efficacy and safety of trastuzumab combined with docetaxel-based chemotherapy in previously treated metastatic gastric carcinoma of Chinese patients with HER2 over-expression. METHODOLOGY: Twenty-two meta-static gastric cancer patients with HER2 over-expression (3+ by immunohistochemistry or HER2 amplification by fluorescence in situ hybridization) previously treated with 5-fluorouracil-based chemotherapy were eligible. Trastuzumab was administrated at 8mg/kg as a loading dose followed by 6mg/kg ev-ery 21 days. Docetaxel-based chemotherapy regimens were also given every 21 days. RESULTS: Median age was 56 years. ECOG performance status was 0-2. Thir-teen patients (59.1%) achieved partial response (PR)and 7 patients (31.8%) had stable disease (SD). Median progression free survival was 6.8 months and the median overall survival was 16.0 months. A patient with 3+ HER2 expression and HER2 gene amplification achieved PR after 6 cycles of combined treatment and received operation. Interestingly, his HER2 expression status in tumor tissue turned into negative after operation and he was still alive without progression until now. Trastuzumab combined with docetaxel-based chemotherapy was well tolerated. Grade 3-4 hematological toxicities were leucopenia (31.8%), neutropenia (18.2%) thrombocytopenia (9.1%) and ane-mia (4.5%). No unexpected toxicities, treatment-related deaths and symptomatic congestive heart failure were observed. CONCLUSIONS: Combinations of trastuzumab plus docetaxel-based regimens were well tolerated and effective in previously treated metastatic gastric cancer of Chinese patients with HER2 over-expression or gene amplification.

[Expressions of CD34 and CD117 in human hepatocellular carcinomas and the clinical significance].

To study the expressions of CD34 and CD117 in the tissues of hepatocelluar carcinoma (HCC) and to explore the relationship with clinical pathology and it's evaluation on the prognosis of HCC patients. The expressions of CD34 and CD117 were examined by two-step methods of PV-9000 of immunohistochemistry in 55 HCC cases, 10 liver cirrhotic specimens and 6 normal liver specimens. Clinical-pathological data, tumor recurrent rate and survival rate after hepatectomy were recorded and analyzed with Fisher's Exact Test, Pearson X2 Test, Kaplan-Meier, Log-Rank Test and Cox Regression. The positive expression of CD34 was found in 65.4% of HCC, 20% of cirrhostic liver specimens and 16.7% of normal liver specimens, respectively. Significant differences found among the three groups, and the CD34 expression was significantly associated with vessel embolus (X2 = 4.000, P = 0.046) and the histological grades (X2 = 11.008, P = 0.001). The positive expression of CD117 was 47.3%, 10% and 0% in HCC, cirrhotic liver specimens and normal liver tissues, respectively, and statistical differences esxisted among the three groups. The CD117 expression was dramatically related to the histological grades (X2 = 5.115, P = 0.024) and clinical stages (X2 = 15.459, P = 0.000). Median disease free survival time after hepatectomy was significantly shorter in the group with positive-expression of CD34 (X2 = 4.105, P = 0.043) and CD117 (X2 = 28.023, P = 0.000) than the negative-expressed groups, respectively. Multivariate analysis showed that CD117 expression status, serum AFP levels and the size of tumor were independently prognostic factors for HCC patients. Tthe results demonstrated that CD34 and CD117 might play an important role in liver carcinogenesis and the progression of HCC, and they might potentially serve as markers for HCC prognosis.

[The relationship between RACK1 expression and clinicopathologic information of esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the expression and relationship of receptor for activated C kinase 1 (RACK1) and clinical characteristics in esophageal squamous cell carcinoma (ESCC). METHODS: Western Blotting was conducted to detect the RACK1 expression in ESCC cell lines. Immunohistochemistry was performed to assay the expression of RACK1 and Ki67 in tumor tissues and adjacent normal epithelium from 113 ESCC patients in tissue microarray. The relationship between the RACK1 level and such clinicopathologic profiles as age, gender, location, smoking, differentiation degree and TNM (tumor, node, metastasis) stage were analyzed. RESULTS: The expression of RACK1 protein was significantly down-regulated in ESCC tissues as compared with the normal adjacent epithelium (χ(2) = 63.363, P < 0.01). An upregulated expression of RACK1 was observed in 72.5% (29/40) ESCC tissues of patients without a smoking history. And it was significantly higher than that in 46.6% (34/73) of patients with a smoking history (χ(2) = 7.040, P = 0.008). In addition, the rate of up-regulated of RACK1 was significantly higher in stage I and II group (63.8%, 44/69) than that in stage III group (43.2%, 19/44) (χ(2) = 4.616, P = 0.032). Moreover, the ESCC tissues with a higher Ki67 score showed a lower level of RACK1 than that with a lower Ki67 score (χ(2) = 8.261, P = 0.016). CONCLUSION: The expression of RACK1 is down-regulated in ESCC tissues and associated with smoking. The expression of RACK1 was associated with smoking, TNM staging and Ki67 score of ESCC.

[Expression of leptin and leptin receptor in hepatocellular carcinoma and the clinicopathological significance].

OBJECTIVE: To investigate the expressions of leptin and leptin receptor in hepatocellular carcinoma (HCC) and explore the clinicopathological significance. METHODS: The expressions of leptin and leptin receptor were examined by immunohistochemistry in 81 HCC patients undergoing curative tumor resection. The correlations between the expression of two biomarkers and the clinicopathological factors were analyzed. RESULTS: The overexpression rate of leptin and leptin receptor in HCC was 56.8% and 35.8%, respectively. No significant correlation was observed between their overexpression (r=0.236, P=0.034). Leptin receptor overexpression was significantly correlated to the tumor size and TNM stage (P<0.05), but not to age, body mass index, α-fetoprotein, hepatitis B surface antigen status, tumor grade, vascular invasion, or liver cirrhosis (P≥0.05). Leptin overexpression showed no significant correlations to the above clinicopathological factors (P≥0.05). CONCLUSION: Leptin receptor overexpression may have an inhibitory effect on hepatocellular carcinoma. The expression status of leptin receptor decides the action of leptin and leptin receptor after their binding.