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Wang H.,Sun Yat Sen University | Wang H.,State Key Laboratory of Oncology | Wang H.,Collaborative Innovation Center for Cancer Medicine | Sun R.,Sun Yat Sen University | And 7 more authors.
Cancer Science | Year: 2013

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) frequently show different clinical and pathological features, which tend to be younger age, better performance status, less tobacco and alcohol consumption, more poorly differentiated histopathology, but usually with better treatment response and prognosis compared with HPV-negative OPSCCs. In tumor tissue, HPV infection is closely correlated with p16INK4A expression, which has been suggested to be a surrogate biomarker of HPV infection. However, there is diversity of sensitivity and specificity about p16INK4A in surrogate detection of HPV status. Herein, we summarize the current knowledge and note some aspects for consideration concerning p16INK4A as a surrogate biomarker for HPV-associated OPSCC. © 2013 Japanese Cancer Association.

Zhao Y.-Y.,State Key Laboratory of Oncology | Zhao Y.-Y.,Sun Yat Sen University | Xue C.,State Key Laboratory of Oncology | Xue C.,Sun Yat Sen University | And 11 more authors.
Journal of Thoracic Oncology | Year: 2012

Introduction: The use of bevacizumab combined with chemotherapy represents a recent advance in clinical oncology for significantly improving the survival of patients who have non-small cell lung cancer (NSCLC). There is an unmet need for biomarkers that can predict response to such treatment and identify patients sensitive to it. Our study was designed to investigate the predictive value of intratumoral microvascular density (MVD) in patients with NSCLC treated with bevacizumab. Methods: Sixteen patients with NSCLC who underwent chemotherapy combined with bevacizumab were included into this study. Paraffin-embedded tumor samples were sectioned and stained immunohistochemically for the blood vessel markers CD34 and CD31 to characterize the intratumoral vasculature. A computerized image analysis program was used to quantitatively calculate the intratumoral MVD. Treatment response was evaluated by computed tomography scanning. Results: Two types of blood vessels, undifferentiated (CD31 +/CD34 -) and differentiated (CD34 +), were identified. A positive correlation was found between the largest percentage of tumor shrinkage and the MVD of undifferentiated (CD31 +/CD34 -) vessels, with Spearman correlation coefficient being 0.576 (p = 0.019). No correlation between tumor shrinkage and differentiated vessel MVD (CD34) was found. Moreover, seven of the eight patients with more undifferentiated vessels showed a partial response, versus only one of the seven patients with fewer undifferentiated vessels (p = 0.009). Conclusions: There are two major types of microvessel in lung cancer vasculature. The MVD of undifferentiated vessels is a favorable predictor for patients with NSCLC treated with a chemotherapy regimen plus bevacizumab, with a higher MVD value correlating with better treatment response. Further studies are needed to verify the predictive role of MVD in treatment of NSCLC with bevacizumab. Copyright © 2011 by the International Association for the Study of Lung Cancer.

Wen J.,University of Houston | Wen J.,State Key Laboratory of Oncology | Wen J.,Sun Yat Sen University | Fu J.-H.,State Key Laboratory of Oncology | And 3 more authors.
Chinese Journal of Cancer | Year: 2011

Lung cancer is the leading cause of cancer death in men and women worldwide, with over a million deaths annually. Tobacco smoke is the major etiologic risk factor for lung cancer in current or previous smokers and has been strongly related to certain types of lung cancer, such as small cell lung carcinoma and squamous cell lung carcinoma. In recent years, there has been an increased incidence of lung adenocarcinoma. This change is strongly associated with changes in smoking behavior and cigarette design. Carcinogens present in tobacco products and their intermediate metabolites can activate multiple signaling pathways that contribute to lung cancer carcinogenesis. In this review, we summarize the smoking-activated signaling pathways involved in lung cancer.

Liu H.,State Key Laboratory of Oncology | Liu H.,Sun Yat Sen University | Lu L.,State Key Laboratory of Oncology | Lu L.,Sun Yat Sen University | And 12 more authors.
Radiotherapy and Oncology | Year: 2011

Purpose: To analyze the clinical implications of metastatic cervical lymph nodes in unresectable thoracic esophageal squamous cell carcinoma (SCC) after concurrent chemoradiotherapy (CRT). Methods and materials: 208 thoracic esophageal SCC patients treated with concurrent CRT were analyzed retrospectively. Patients were divided into 3 groups according to different status of metastatic cervical lymph nodes: 1. CLN(-), no evidence of metastatic cervical lymph nodes; 2. CPLN(+), evidence of enlarged cervical paraesophageal lymph node without any other metastatic cervical lymph nodes; 3. OCLN(+), any other situations of enlarged cervical lymph nodes. The prognostic factors were examined univariately, then selected for inclusion in a multivariate Cox regression model. Results: Three-year OS of CLN(-),CPLN(+), and OCLN(+) groups were 39%, 33%, and 15% (logrank p = 0.001). On univariate analysis, variables significantly associated with OS included sex, primary esophageal tumor location, length and cervical nodal disease. On multivariate analysis, primary tumor location (HR1.5, 95%CI 1.1-1.9, p = 0.005), tumor length (HR1.5, 95%CI 1.1-2.0, p = 0.010) and cervical nodal disease (HR1.2, 95%CI 1.0-1.5, p = 0.014) were prognostic factors on OS. Conclusions: (1) Primary tumor location, tumor length, and cervical nodal disease were significant prognostic factors on OS in esophageal SCC patients. (2) Patients with CPLN(+) disease tended to have a potential better long-term survival than those with OCLN(+) disease, and metastatic CPLN could be considered as local disease. The survival benefit in CPLN(+) subgroup might be contributed by the patients who presented with upper third thoracic tumors and shorter tumor length. Further investigation is needed. © 2011 Elsevier Ireland Ltd. All rights reserved.

Xie F.Y.,State Key Laboratory of Oncology
Chinese journal of cancer | Year: 2010

It is controversial for the irradiation level and dose of the regional prevention for naspharyngeal cancer (NPC) with one or both cervical lymph node-negative neck. The study was to analyze the proophylactic irradiation of cervical lymph nodes for Stage -N0 NPC patients. From January 2002 and December 2004, 205 NPC patients with negative lymphadenopathy diagnosed by imaging, were retrospectively analyzed. Before treatment, each patient underwent CT or MRI. Facial-cervical portals and 6-8 MV photons were used in radiotherapy. Doses applied were 60-80 Gy to the nasopharynx and 46-64 Gy to the neck without lymphadenopathy. Consecutive radiotherapy was performed employing conventional fractionation of 2 Gy/fraction, once a day, for a total of five fractions per week. Chemotherapy was administered to 60 patients. Median follow-up was 44 months. The survival function was calculated according to the Kaplan-Meier method. A log-rank test was used to compare the differences in survival. The Cox proportional hazards model was used for multivariate analysis. A total of 205 patients with stage-N0 NPC were divided into an upper-neck irradiation group and an entire-neck group. The 3-year overall survival rate (OS) was 92.9% and the 3-year disease-free survival rate (DFS) was 91.9%. A total of 88 patients received irradiation to the upper neck and 117 to the entire neck. The rate of regional failure for the upper-neck group and the entire-neck group were 2.27% and 0%, respectively (P>0.05). The rates of regional failure in patients with T1-, T2-, T3- and T4-stage disease were 0, 3.08%, 0, and 0, respectively (P>0.05). The rates of regional failure in the patients both without and with local failure were 1.03% and 0, respectively (P>0.05). The 1-and 3-year OS for the upper-neck group were 97.7% and 94.2%, and the 1- and 3-year OS for the entire-neck group were 97.4% and 91.9% (P=0.950). The 1- and 3-year DFS for the upper-neck group were 96.6% and 92.9%, and the 1- and 3-year DFS for the entire-neck group were 95.6% and 90.9% (P= 0.730). In multivariate analysis, sex (P=0.039) and T stage (P=0.004) were independent prognosis factors for patients with stage-N0 NPC. Prophylactic irradiation to the upper neck does not influence regional failure or long-term survival in the patients with stage-N0 NPC. Radiotherapy to the upper neck (levels II, III, VA) is recommended for the patients with stage-N0 NPC. Involvement of the parapharyngeal space, T stage, and the rates of local failure do not influence regional failure in these patients. Sex and T stage were independent prognosis factors of stage-N0 NPC patients.

Huang P.Z.,State Key Laboratory of Oncology
Chinese journal of cancer | Year: 2010

Recently, many studies have focused on stem cells in hepatocellular carcinoma (HCC) and found some stem cell markers in HCC, which are associated with the prognosis. OCT4, as a member of the POU transcription factor family, is a key factor to maintain self-renewal and pluripotency of embryonic stem cells (ESCs). This study was to explore the expression of the ESCs marker OCT4A in HCC, and its correlations with clinicopathologic features and prognosis of HCC. OCT4A mRNA expression was detected in five liver cancer cell lines (SMMC-7721, BEL-7402, Hep-G2, MHCC97-L, and MHCC97-H), one immortalized liver cell line L-O2, tumor tissues with matched non-neoplastic liver tissues in 107 HCC patients, and normal liver tissues of 20 cases using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The correlations between OCT4A mRNA and clinicopathologic features and prognosis of HCC were analyzed. OCT4A mRNA was detected in SMMC-7721, BEL-7402, Hep-G2, MHCC-97L, and MHCC-97H cells, but not in L-O2 cells. The positive rate of OCT4A mRNA expression was significantly higher in the HCC tissues than in the non-neoplastic liver tissues (72.0% vs. 30.8%, P<0.001). No OCT4A mRNA expression was found in the normal liver tissues. OCT4A mRNA expression was correlated with the tumor size, vascular invasion, and TNM stage (P<0.05). Kaplan-Meier survival curves showed that patients with positive expression of OCT4A mRNA had lower overall survival and disease-free survival rates. OCT4A mRNA, which is highly expressed in a subset of liver cancer cell lines and HCC tissues, may be involved in the carcinogenesis of HCC. OCT4A mRNA may be a valuable biomarker for assessing the prognosis of HCC.

Li J.X.,State Key Laboratory of Oncology
Chinese journal of cancer | Year: 2010

At present, although appropriate radiotherapy and combined treatments are widely used for the patients with primary nasopharyngeal carcinoma (NPC), local or regional recurrence rates are still high. According to clinical performance, pathology, and diagnostic imaging of the patients with the first recurrence of NPC, this study analyzed the clinical features of recurrent NPC to provide a reference for tracking the rules of recurrence after the treatment of patients with NPC. Clinical data of 337 patients diagnosed with recurrent NPC for the first time were collected. The diagnoses were based on pathology and/or imaging and the patients were treated at the Sun Yat-sen University Cancer Center between January 1999 and December 2004. Data used for statistical analysis included clinical performance during the patient visit, the extension of the invasion as shown on imaging, pathologic features, Epstein-Barr virus (EBV) serology, restaging, etc. Patients were staged according to the system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in 2002. Patients with diseases at stages I/II accounted for 25.2%, while those with stage III/IV accounted for 74.8%. The median interval of relapse was 25 months. Patients had local recurrence (69.4%), regional recurrence (4.5%), or both (26.1%). Epistaxis and headache were the most common symptoms. Abduct dysfunction and facial numbness induced by cranial nerve damage were the most common signs. The probability of invasion of structures adjacent to the nasopharynx, such as the oropharynx, the prestyloid space, and the carotid sheath area, was low in patients with recurrent NPC. By contrast, the probability of invasion of structures far from the nasopharynx, such as the base of the skull, the paranasal sinuses, cranial nerves, the cavernous sinus, the brain, the pterygopalatine fossa, the infratemporal fossa, the orbital apex, and the soft palate, was higher in recurrent NPC. The most common interval of relapse is about 2 years. The relapsed disease is usually more widespread and located deeper. Most recurrent NPC is advanced disease.

Zheng B.,State Key Laboratory of Oncology
Chinese journal of cancer | Year: 2010

The incidence of adenocarcinoma of the cardia has recently increased. This study compared the clinicopathology and prognosis of patients with gastric cardia adenocarcinoma in different periods between 1984 and 2003. A total of 589 patients with pathologically confirmed gastric cardia adenocarcinoma hospitalized in Sun Yat-sen University Cancer Center between 1984 and 2003 were divided into 5-year groups. Retrospective analysis of clinical and prognostic characteristics between the different 5-year groups was conducted. The number of hospitalized patients increased by 134.5%, with an annual increase of 4.6%. Median age was 60 years, with an increase of 5 years. Patients aged between 55 years and 64 years decreased, while patients aged > or = 65 years increased. The male-to-female ratio was 2.88:1, with no significant change. The rates of patients with the stage-I and -II disease changed insignificantly, while patients with stage-III disease increased, and patients with stage-I disease decreased. The 5-year survival rate of all the patients was 28.5%, which increased from 20.9% between 1984 and 1993 to 35.5% between 1994 to 2003. During the past 20 years, associated with the upward-trending incidence of gastric cardia adenocarcinoma, the admission rate at our hospital of patients with the tumor increased. The median age of the patients also increased. The ratio of men to women had no significant change. The proportion of patients with late-stage disease decreased and prognosis has improved.

Cao Y.,State Key Laboratory of Oncology
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2012

C-reactive protein (CRP) is an acute-phase reactant that is a promising biomarker in patients with cancer of many kinds. The aim of this retrospective study was to evaluate significant changes in CRP levels as a parameter for the response effect and long-term survival of patients with diffuse large B cell lymphoma (DLBCL). Serum CRP data were collected in 94 patients with DLBCL from October 2006 to August 2009 in Cancer Center, Sun Yat-Sen University. Results were correlated with clinical data. The median CRP serum level in patients with DLBCL was 30.91 ± 53.35 in male and 22.39 ± 29.89 mg/L in female. Base line CRP levels were correlated with International Prognostic Index (IPI) scores (p = 0.03). Among the patients with an IPI score of 1-2, base line CRP levels were correlated with long-term survival (p = 0.001). Base line CRP levels were also correlated with OS (p = 0.001) and varied with different clinical stages (p = 0.03). The corresponding CRP levels in the patients with 2 cycles of chemotherapy were correlated with short-term treatment response (p = 0.003) and OS (p = 0.04) or TTP (p = 0.03). CRP serum levels can be used as additional prognostic parameter in patients with diffuse large B cell type lymphoma.

CT-guided microwave coagulation is a minimally invasive surgery for patients with liver cancer. Total intravenous anesthesia with propofol and fentanyl is commonly used. The depth of anesthesia during microwave coagulation for liver cancer is still monitored by clinical signs. There are few subjective and effective indicators. This study explored the application of Narcotrend-assisted "depth of anesthesia" monitoring on microwave coagulation for patients with liver cancer during total intravenous anesthesia with propofol and fentanyl. Forty liver cancer patients underwent CT-guided microwave coagulation were randomly assigned to receive Narcotrend index monitoring or standard clinical monitoring for depth of anesthesia with 20 patients in each group. All patients received total intravenous anesthesia with propofol and fentanyl. The depth of anesthesia for patients in the Narcotrend group was measured according to a Narcotrend index, which was maintained between D2 and E0. The depth of anesthesia for those in the standard clinical practice group was measured according to heart rate, mean arterial pressure, and patient movement. Changes of hemodynamics, the duration of the emergence from anesthesia, and the recovery of orientation were recorded. The doses of propofol and fentanyl, postoperative visual analogue scores (VAS), and the incidence of postoperative nausea and vomiting were also recorded. There was no significant alteration in heart rate or mean arterial pressure between the two groups. Compared with other anesthetic stages, both heart rate and mean arterial pressure decreased during the induction of the anesthesia in the two groups(P<0.05). The doses of propofol were higher in the standard clinical practice group than in the Narcotrend group [(460+/-30) mg vs. (380+/-35) mg, P<0.01]. The duration of emergence and orientation were longer in the standard clinical practice group than in the Narcotrend group [(9.5+/-2.9) min vs. (4.9+/-2.2) min, P<0.01; (12.2+/-3.5) min vs. (6.6+/-3.2) min, P<0.01, respectively]. There was no difference in the dosage of fentanyl, VAS, or the incidence of postoperative nausea or vomiting between the two groups (P>0.05). For patients with liver cancer, monitoring the depth of anesthesia with Narcotrend on microwave coagulation can contribute to lower dosage of propofol and shorten duration of recovery during total intravenous anesthesia with propofol and fentanyl.

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