Selected proliferation markers correlated with dynamics of growth in colorectal cancer.

For treatment of metastatic colorectal cancer, the dynamics of tumor growth is an important factor for treatment decision. However, it is difficult to evaluate the dynamics of tumor growth, especially those of synchronous metastatic diseases. This study aimed to find some indicators related to tumor proliferation to judge the dynamics of tumor progression. The pathological reports and clinical data of 1205 patients with metastatic colorectal cancer were retrospectively reviewed; 75 patients with known relapse time after radical resection were included, and the expression of proliferation-associated proteins was detected by immunohistochemistry. Relapse-free time (RFT) from radical resection to relapse was obtained to analyze the relationship with expression of these factors. Kaplan-Meier univariate analysis showed that the overexpression of cyclin D1 and epidermal growth factor receptor (EGFR) and late pathological stage after surgery indicated shorter RFT. Multivariate analysis showed that EGFR and the stage were independent predictors of RFT. Expression of EGFR and cyclin D1 and the pathological stage were included as combination risk factors for RFT analysis; more risk factors were correlated with shorter RFT. EGFR and cyclin D1 seemed to be indicators of the dynamics of tumor growth, and overexpression of those molecules may suggest rapid growth and poor prognosis.

Hepatitis B virus reactivation and hepatitis in gastrointestinal cancer patients after chemotherapy.

PURPOSE: The objectives of this study were to investigate the incidences of hepatitis B virus (HBV) reactivation and hepatitis in gastrointestinal cancer patients with positive hepatitis B surface antigen (HBsAg) after chemotherapy and assess the effect of antiviral therapy on preventing HBV reactivation and hepatitis. METHODS: The medical records of gastric or colorectal cancer patients with positive HBsAg undergoing chemotherapy in West China Hospital were reviewed from January 2009 to August 2014. RESULTS: One hundred and fifty-six patients were included. Seventy-six patients had no records of the baseline HBV DNA copy (bHDC) and received no antiviral therapy. Of 80 patients with known bHDCs, 39 patients received antiviral therapy. The incidence of HBV reactivation was 14.6% in the non-antiviral group with known bHDCs (n = 41), compared with 0% in the antiviral group (P = 0.039). Compared with 12.8% in the antiviral group (P = 0.034), 29.9% of patients suffered from hepatitis in the total non-antiviral group (n = 117). More patients with moderate/severe hepatitis were seen in the non-antiviral group (P = 0.027). Non-antiviral therapy was the only risk factor for hepatitis in multivariate analysis (HR 3.195, 95% CI 1.117-10.989; P = 0.043). CONCLUSIONS: HBV reactivation and hepatitis occurred in a significant proportion of gastrointestinal cancer patients with positive HBsAg who received chemotherapy. Antiviral therapy could reduce the incidences of HBV reactivation and hepatitis.

Expression characteristics of proteins of the insulin-like growth factor axis in non-small cell lung cancer patients with preexisting type 2 diabetes mellitus.

BACKGROUND: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. METHODS: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. RESULTS: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. CONCLUSION: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

Serum carbohydrate antigen 19-9 as an indicator of liver metastasis in colorectal carcinoma cases.

PURPOSE: The liver is the organ to which colorectal carcinomas (CRCs) most commonly metastasize, and surgical resection has been established as the most effective and potentially curative treatment for CRC with liver metastasis (LM). Therefore, surveillance of LM is vital for improvement of prognosis of CRC patients. In this study, we aimed to explore the potential value of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), and marker enzymes in indicating LM with CRC. METHODS: Three groups of eligible patients with metastatic cancers were retrospectively included: CRC patients with LM (CRC-LM) or without LM (CRC- NLM), and non-CRC patients with LM (NCRC-LM). All metastatic lesions were identified by CT or MRI. Data on characteristics of the patients, the primary site, the locations of metastasis, CA 19-9, CEA, and biochemical parameters were collected for analysis. RESULTS: A total of 493 patients were retrospectively included. More alcohol consumption was found in CRC-LM than CRC-NLM. Some biochemical enzymes were found to be significantly higher in groups with LM than without (CRC-LM or NCRC-LM v.s CRC-NLM). Both CEA and CA 19-9 were much higher in CRC-LM than CRC-NLM or NCRC-LM. For CRC patients, CA 19-9, γ-glutamyl transpeptidase, CEA and alcohol consumption were identified as independent factors associated with LM. CONCLUSION: Our analysis suggested the CA 19-9 might be a potential valuable indicator for LM of CRC in the clinic.

The upregulation of dihydropyrimidine dehydrogenase in liver is involved in acquired resistance to 5-fluorouracil.

BACKGROUND: Acquired resistance to 5-fluorouracil (5-FU) is one of the important reasons for failure in 5-FU-based chemotherapy. The upregulation of dihydropyrimidine dehydrogenase (DPD) in tumours was reported as an important factor for acquired 5-FU resistance. The aim of this study is to examine whether intra-hepatic DPD was involved in acquired 5-FU resistance. METHODS: HT-29 human colorectal xenograft tumours were established in nude mice. After long-term exposure to 5-FU, some of the tumour became "resistant" and the others remained "sensitive" to 5-FU. DPD expression levels in the livers and tumours of "resistant", "sensitive" or untreated mice were examined, and pharmacokinetics of 5-FU in rats' plasma were investigated. Gimeracil, a DPD inhibitor, was checked whether it could reverse the reduced bioavailability of 5-FU. RESULTS: DPD expression was upregulated obviously in tumours of "resistant" mice as reported previously. Importantly, DPD expression was also upregulated significantly in livers of "resistant" mice, compared with those of "sensitive" or untreated mice. Furthermore, the upregulation of DPD expression in livers led to accelerated metabolism of 5-FU. Gimeracil was found to reverse the reduced serum 5-FU concentration. The cultured tumour cells from 5-FU treated mice showed relative sensitivity to higher concentration of 5-FU, even the "resistant" tumour cells. CONCLUSION: Our study suggested that the upregulation of DPD in liver may be involved in acquired resistance to 5-FU, and DPD inhibitors or increasing 5-FU dosage may have potential application in overcoming 5-FU acquired resistance.

Factors potentially associated with chemotherapy-induced anemia in patients with solid cancers.

PURPOSE: Chemotherapy-induced anemia (CIA) is one of the most important causes of anemia in cancer patients. This study was conducted to describe the prevalence and characteristics of CIA in solid cancer patients in the Chinese population, and to explore the relationship of white blood cell (WBC) or platelet decrease with CIA. METHODS: Data on age, gender, tumor diagnosis, anti-cancer treatment and blood cell analyses were available from 220 untreated non-anemic cancer patients who received at least 2 cycles of chemotherapy, and the data were analyzed to assess their relationship with CIA or its severity. RESULTS: 139 patients (63.2%) presented anemia, most being Grade 1 or 2. Esophageal and lung cancers were associated with a high prevalence. G3/4 leucopenia and decrease of platelets were identified as independent risk factors for the occurrence of CIA. Moreover, G3/4 leucopenia, decrease of platelet and G3/4 thrombocytopenia were found to be also associated with the severity of CIA. Cisplatin-containing regimens were a main potential factor in causing CIA, although significant association was only found on univariate analysis. CONCLUSION: Anemia or decrease in hemoglobin are common in Chinese cancer patients receiving chemotherapy. Cisplatin-containing regimens might be an important factor influencing the occurrence of CIA. Our analysis firstly described some risk factors, such as decrease of platelets or WBCs, severity of leucopenia or thrombocytopenia, associated with the occurrence and severity of CIA.