High-grade transformation of head and neck adenoid cystic carcinoma demonstrates distinctive clinicopathological features and an unfavorable prognosis: a matched case-control study of the largest series in China.

PURPOSE: Amidst the rarity of High-grade transformation (HGT) in adenoid cystic carcinoma (ACC), this study offers unprecedented insights into its aggressive nature and clinical implications. METHODS: A 1:1 match comparison between 23 HGT patients and non-HGT counterparts was extracted from 412 ACC cases, focusing on dissecting distinctive clinicopathological features and prognostic outcomes. RESULTS: The predominant sites of HGT were the sinonasal and lacrimal glands (30.4% each). Notably, the solid subtype was the most prevalent pattern within HGT, accounting for 69.6% of cases. Compared to non-HGT, the HGT cohort exhibited significantly higher rates of lymph node metastasis (39.1% vs. 8.7%; P < 0.05), perineural invasion (60.9% vs. 26.1%; P < 0.05), and increased Ki-67 proliferation index (35.0% vs. 10.0%; P < 0.05). Moreover, HGT regions typically showed reduced or absent p63 expression, along with high-grade pathomorphology. HGT was associated with increased recurrence (55.0%) and distant metastasis (78.3%), leading to an average survival of 35.9 months and a 3-years mortality rate of 35.0%. Overall and progression-free survival rates were significantly decreased in the HGT group. CONCLUSION: This study represents the largest single-center cohort of HGT cases to our knowledge, highlighting its frequent occurrence in the sinonasal and lacrimal glands and association with poorer outcomes. The findings support classifying HGT in ACC as Grade 4, reflecting its severity.

The effect of influenza A (H1N1) pdm09 virus infection on cytokine production and gene expression in BV2 microglial cells.

Acute influenza infection has been reported to be associated with neurological symptoms such as influenza-associated encephalopathy (IAE). Although the pathophysiology of this condition remain unclear, neuroinflammation and associated alterations in the central nervous system (CNS) are usually induced. Microglia (MGs), CNS-resident macrophages, are generally the first cells to be activated in response to brain infection or damage. We performed reverse transcriptase droplet digital PCR (RT-ddPCR) and luminex assays to investigate virus proliferation and immune reactions in BV2 MGs infected with influenza A(H1N1)pdm09 virus. Furthermore, isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics methods were used to investigate the dynamic change in the protein expression profile in BV2 MGs to gain insight into the CNS response to influenza A (H1N1) pdm09 infection. Our results showed that the influenza A(H1N1)pdm09 virus was replicative and productive in BV2 MG cells, which produced cytokines such as interleukin (IL)-1ß, IL-6, tumour necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1. The expression of osteopontin (OPN) in the influenza A (H1N1) pdm09-infected BV2 MGs was upregulated at 16 and 32 h post-infection (hpi) compared to that in the control group, resulting in aggravated brain damage and inflammation. Our study indicates that OPN signalling might provide new insights into the treatment of CNS injury and neurodegenerative diseases in IAE.

[A method for reliable detection of genomic point mutations based on single-cell target-sequencing].

The analysis of genomic point mutations is one of the research strategies to explore the clonal evolution of tumor cells. At present, clonal evolution of tumor cells is mainly determined by bulk sampling and sequencing of different sections of the tumor. Since this approach analyzes a mixture of different cell types, it may not accurately represent the clonal evolution of specific tumor cell populations and likely miss low frequency mutations, especially when the sequencing depths are not sufficient. To address this issue, we have developed a strategy to analyze genomic point mutations from prostate basal cell carcinoma (BCC) tissues at single-cell resolution. Firstly, we optimized the single-cell whole genome amplification procedure with HepG2 cells. Then the single cells from BCC tissue were captured by a microfluidic chip of Fluidigm and processed for whole-genome amplification. Both SCUBE3 and MST1L genomic mutations were obtained by whole exome sequencing. Finally, we examined the genomic mutations through single-cell targeted amplification and Sanger sequencing. The established method successfully reconfirmed the mutations of SCUBE3 and MST1L in BCC at single cell level. The strategy established in this study could provide a useful tool for determining the clonal evolution of tumor cells based on genomic mutations at single-cell resolution.

SKA3 promotes lung adenocarcinoma metastasis through the EGFR-PI3K-Akt axis.

The processes that lead to lung adenocarcinoma (LUAD) metastasis are poorly characterized. Spindle and kinetochore associated complex subunit 3 (SKA3) plays a key role in cervical cancer development, but its contribution to LUAD is unknown. Here, we found that SKA3 is overexpressed in LUAD and its expression correlates with lymph node metastasis and poor prognosis. SKA3 silencing experiments identified SKA3 as an oncogene that promotes the metastasis of LUAD cell lines and tissues. SKA3 was found to induce the expression of matrix metalloproteinase (MMP)-2, -7, and -9, which activate PI3K-AKT. SKA3 was also found to bind and activate EGFR to activate PI3K-AKT. In summary, we identify a role for SKA3 in LUAD metastasis through its ability to bind EFGR and activate PI3K-AKT signaling.

Serum angiopoietin-2 concentrations of post-PCI are correlated with the parameters of renal function in patients with coronary artery disease.

Patients with coronary artery disease (CAD) frequently have comorbidity of chronic kidney disease (CKD). Their renal function may deteriorate because of the use of contrast agent after percutaneous coronary intervention (PCI). Angiopoietin-2 (Ang-2), which is highly expressed in the site of angiogenesis, plays an important role in both CAD and CKD. This study aimed to investigate the relation of serum Ang-2 concentrations with the renal function after PCI.This study enrolled 57 patients with CAD undergoing PCI. Blood samples for Ang-2 were collected in the first morning after admission and within 24 to 48 h after PCI. The parameters of renal function (serum creatinine, cystatin C and eGFR) were tested on the first day after admission and within 72 h after PCI.Overall, serum Ang-2 levels of post-PCI were significantly lower than those of pre-PCI [median, 1733 (IQR, 1100-2568) vs median, 2523 (IQR, 1702-3640) pg/mL; P < .001]. However, in patients with CKD (eGFR < 60 mL/min/1.73 m), there was no significant difference between serum Ang-2 levels of post-PCI and those of pre-PCI [median, 2851 (IQR, 1720-4286) vs. median, 2492 (IQR, 1434-4994) pg/mL; P = .925]. In addition, serum Ang-2 levels of post-PCI, but not pre-PCI, were significantly correlated with the post-PCI parameters of renal function.Serum Ang-2 concentrations of post-PCI are closely related to renal function in patients with CAD. It may have potential to be the early biomarker of contrast-induced nephropathy in the future.

An unusual intragenic promoter of PIWIL2 contributes to aberrant activation of oncogenic PL2L60.

PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand. Chromatin immunoprecipitation analysis demonstrates that both the HLF and polymerase II (Pol II), a hallmark of active promoters, directly bind to the sequence, although STAT3 does not. Knockdown of HLF and STAT3 alone or both by RNA interference significantly reduced both promoter activity and the PL2L60 protein expression, although there is no additive effect. The expression of PL2L60 proteins was enhanced when host gene Piwil2 was genetically disrupted in a murine cell model. Taken together, we have identified a PL2L60-specific intragenic promoter in the host gene of PIWIL2, which is interdependently activated by HLF and STAT3 through steric interaction. This activation is dependent on cellular milieu rather than the integrity of host gene PIWIL2, highlighting a novel, important mechanism for a cancer-causing gene to be activated during tumorigenesis.

A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy-A single-institution experience.

BACKGROUND: Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin-preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as "T1G3." OBJECTIVE: To evaluate the characteristics and the long-term outcome of GC adjuvant chemotherapy in T1G3 bladder cancer after transurethral resection of bladder tumor (TURBT). MATERIALS AND METHODS: We retrospectively reviewed 48 patients who were newly diagnosed with T1G3 bladder cancer between January 2009 and December 2012. A total of 48 patients received 4 cycles of GC adjuvant chemotherapy after TURBT. One month after 4 cycles of GC adjuvant chemotherapy, response was evaluated by re-TURBT. Median follow-up was 59.5 (range: 18-70) months, all patients have been observed for more than 3 years. Salvage cystectomy was recommended for patients with persistent disease and for tumor progression after initial complete response. RESULT: Complete response was achieved in 44 (91.7%) patients. Of complete responders, 5 patients experienced recurrence and 5 patients showed progression. The progression rate and disease-specific survival rate were 10.4% and 91.7% at 3 years, respectively. More than 80% of survivors preserved their bladder. Kaplan-Meier curves showed that concomitant carcinoma in situ (CIS) was the only factor that had an influence on progression-free survival (P = 0.022) and disease-specific survival (P = 0.017). Concomitant CIS was the prognostic factor for progression rate and disease-specific survival rate at 3 years (P = 0.008 and P = 0.035). CONCLUSION: GC adjuvant chemotherapy is a safe conservative treatment for T1G3 bladder cancer, but effective is really a phase II study. Patients with T1G3 bladder cancer with concomitant CIS should be treated more aggressively because of the high risk of progression.

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies.

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis (PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of < 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases I, II and III clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.

Metformin can block precancerous progression to invasive tumors of bladder through inhibiting STAT3-mediated signaling pathways.

BACKGROUND: Metformin is the first line of oral antidiabetic drug in the biguanide class for treatment of type 2 diabetes. Increasing evidence has suggested that it is a potential anti-tumor drug. However, the mechanisms underlying inhibiting tumor development remain elusive, especially in bladder tumors. METHODS: T24 and J82 cell lines were used as an in vitro model, and 24 female SD rats were used to build an N-methyl-N-nitrosourea (MNU)-induced orthotopic rat bladder cancer model. Transfection of lentivirus-based shRNA was used to construct the STAT3-KNOCKDOWN T24 cell line. After metformin treatment, the viability of bladde cancer cells was determined by CCK8. Cell cycle distribution and apoptosis were assessed by flow cytometry. The migration and invasion abilities of cells were evaluated by wound healing and transwell asssays. The inactivation of stat3 pahtway was examined by qRTPCR, western blot and Immunofluorescence. RESULTS: Metformin can effectively inhibit precancerous progression to invasive cancer in an MNU-induced rat orthotopic bladder tumor model, although it could not completely suppress normal cells transforming into tumor cells. While the MNU could induce 50 % rats (4/8) to develop invasive bladder cancers, the rats co-administrated with metformin failed to develop invasive tumors but retained at precancerous or non-invasive stages, exhibiting as dysplasia, papillary tumor and/or carcinoma in situ (CIS). Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin. In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines. CONCLUSIONS: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.

Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer.

BACKGROUND AND OBJECTIVE: High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. HMGB1 overexpression has been reported in a variety of human cancers. However, the clinical significance of HMGB1 expression in bladder cancer (BC) remains unclear. This study is aimed to investigate the correlations between HMGB1 expression and prognosis in patients with BC. METHODS: HMGB1 protein expression in 164 primary BC tissue specimens was analyzed by immunohistochemistry, and its association with clinicopathologic factors and prognosis was also analyzed. RESULTS: HMGB1 protein had high expression in 87 of 164 cases of BC (53%). HMGB1 overexpression was significantly associated with tumor grade (P < 0.001), and stage (P = 0.001). The Kaplan-Meier survival analysis demonstrated that HMGB1 expression was significantly associated with shorter disease-free survival and overall survival (both P < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with BC. CONCLUSIONS: HMGB1 might be a new molecular marker to predict the prognosis of patients with BC.

UHRF1 is associated with tumor recurrence in non-muscle-invasive bladder cancer.

Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is a novel anti-apoptotic gene, and overexpression of UHRF1 is involved in tumorigenicity. Here, immunohistochemistry was used to detect UHRF1 expression in non-muscle-invasive bladder cancer (NMIBC), and these data were examined for correlation with clinicopathological parameters and prognosis. The UHRF1 expression rate was 49.2% in a total of 118 bladder cancer tissues, which was significantly higher than in normal tissues, and UHRF1 expression has a significantly positive correlation with tumor grade (P = 0.027) and recurrence (P = 0.013). Survival analysis showed that UHRF1 high expression patients' mean survival time (42.59 months) was significantly shorter than that (71.36 months) of UHRF1 low expression patients (P = 0.0002). Multivariate analysis showed that UHRF1 overexpression was an independent prognostic factor for tumor recurrence (P < 0.0001). So UHRF1 may be a molecular marker to predict the recurrence of NMIBC.

Screening the gastric cancer related tumor markers from multi-tumor markers protein chip with kappa coefficient and cost-effectiveness analysis.

BACKGROUND/AIMS: To retrospectively evaluate the clinical values of C12 multi-tumor markers protein chip system in gastric cancer (GC) and screen for GC related tumor markers so as to provide a theoretical base for the establishment of GC diagnostic biochips. METHODOLOGY: The sera of 156 GC patients were detected for 12 common tumor markers using the C12 tumor markers protein chip. GC related parameters were analyzed by Kappa test and cost-effectiveness analysis to find the most optimal tumor marker combination. RESULTS: Carbohydrate antigen (CA) 19-9 (20.5%), CA242 (19.9%), carcinoembryonic antigen (CEA, 17.3%), CA125 (7.1%) were major tumor markers increased among the 156 GC patients. Kappa test revealed 6 tumor marker combinations having strong consistency with the detection results of C12 tumor markers proteinchip, and CA19-9 plus CEA proved to be the best combination by cost-effectiveness analysis. CONCLUSIONS: C12 tumor markers protein chip system had limited value in the diagnosis of GC, and the design of chip was too complicated and costly for widespread screening among the high risk populations. Searching for new GC biomarkers and designing small diagnostic chip could significantly enhance the clinical value of tumor markers in terms of diagnostic rate and practical utility.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.

BACKGROUND: This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer. METHODS: Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60-90 min. The primary end point was overall survival, and the secondary end points were safety profiles. RESULTS: Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2-36 (median 15) in the CRS + HIPEC and 3-23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0-1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5-83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8-8.2 months) in CRS and 11.0 months (95% confidence interval 10.0-11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0-1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival. CONCLUSIONS: For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.

Postoperative recurrence in gastric cancer: analysis of 59 cases.

BACKGROUND/AIMS: Gastric cancer (GC) is the leading cause of death in China. Although surgery based comprehensive treatment is the best approach to improve survival, postoperative recurrence is a major problem. This study was aimed to find out the relationship of cancer recurrence with major clinico-pathological factors, with special attention focused on time of recurrence. METHODOLOGY: Data of 59 recurrences after surgery among 286 GC patients were systemically collected and analyzed. Time of recurrence, the relationship between clinical stages and time of recurrence, and between number of adjuvant chemotherapy cycles and time of recurrence were evaluated. RESULTS: 76.3% (45/59) recurrence happened within 1 year after surgery. Median time to recurrence was 7 months. Most recurrences were locoregional recurrence (57.6%). The differences in time of recurrence among stage I, stage II, stage III and stage IV were statistically not significant (p > 0.05, Kruskal-Wallis Test). There were significant differences among different adjuvant chemotherapy cycles for time to recurrence (p = 0.014, Kruskal-Wallis Test). CONCLUSION: Close monitoring and active followup of patients with GC should be conducted over the first 2 years after operation. Adjuvant chemotherapy could prolong recurrence-free survival.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival in selected patients with peritoneal carcinomatosis from abdominal and pelvic malignancies: results of 21 cases.

We evaluated the perioperative safety profile and efficacy of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in 21 patients with peritoneal carcinomatosis (PC) from gastrointestinal and gynecological cancers. Twenty-one patients with PC (12 gastric cancer, 5 colorectal cancer, 2 ovarian cancer, 1 pseudomyxoma peritonei, 1 malignant mesothelioma) were treated with CRS + HIPEC with hydroxycamptothecin 20 mg and mitomycin C 30 mg in 12,000 mL of normal saline at 43 +/- .5 degrees C for 60 to 90 minutes. Vital signs were recorded for 5 days after surgery. We analyzed the following: local and systemic infections; gastrointestinal function recovery; hematological, hepatic, and renal parameters; wound healing time; adverse events; survival; and quality of life. The PC index was 2 to 33 (median, 11), the duration of operation 4 to 10 h (median, 8 h), and the highest temperature during 5 postoperative days 38.1 degrees C. Two patients developed generalized edema and were successfully treated. Five patients developed hypoproteinemia on day 1 after surgery. All routine blood tests checked at 1 week after surgery were normal. Time of gastric tube removal was 2 to 7 days. Liquid food intake time was 3 to 8 days. Time of removal of stitches was 8 to 18 days. No local or systemic infections, wound disruption, or other clinically important adverse events occurred. The follow-up was 8 to 43 months (median, 22.5 months). Eleven patients died, three survived with tumor, and seven survived free of tumor. CRS + HIPEC was well tolerated in our selected patients with PC, some of whom had improved survival.

Evaluation of tumor markers biochip C12 system in the diagnosis of gastric cancer and the strategies for improvement: analysis of 100 cases.

BACKGROUND/AIMS: A C12 biochip system using 12 tumor markers has been developed in China for serum diagnosis of common cancers. This work is to evaluate this C12 system in the diagnosis of gastric cancer. METHODOLOGY: Sera from 100 gastric carcinoma patients were screened for 12 tumor markers including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 19-9, carbohydrate antigen 242, cancer antigen 15-3, cancer antigen 125, prostate specific antigen, free-PSA, neuron-specific enolase, human chorionic gonagotropin-beta, human growth hormone, and ferritin, using the C12 biochip system. The most relevant tumor marker and the contribution of the tumor markers to the improvement of diagnosis were determined. RESULTS: The overall diagnostic rate of C12 biochip system was 37%, and 7.8%, 29.4%, 35.5% and 50%, respectively, for stages I, II, III and IV patients. The differences in diagnostic rates between stage I (7.8%) and stage IV (50%) reached statistical significance (chi-square test, Chi2=7.20, p<0.01). Among all the 12 markers, carbohydrate antigen 19-9 had the highest positive rate up to 23%, against which any form of combinations of 5 most relevant tumor markers (2, 3, 4 or 5 markers combined) could not significantly improve the diagnostic rate. CONCLUSIONS: The C12 biochip system has some value in the diagnosis of advanced stage gastric cancer, but less sensitive in early gastric cancer.

Value of tumor markers in diagnosing and monitoring colorectal cancer and strategies for further improvement: analysis of 130 cases.

BACKGROUND & OBJECTIVE: Measurement of blood tumor markers is the most widely used and convenient method for the diagnosis of colorectal cancer(CRC). This study was to evaluate the diagnostic value of a biochip diagnostic system C12 in the diagnosis of CRC. METHODS: Twelve tumor markers were detected in the sera of 130 pathologically confirmed CRC patients, including carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242), cancer antigen 15-3 (CA15-3), cancer antigen 125 (CA125), prostate specific antigen (PSA), free-PSA(f-PSA), neuron-specific enolase (NSE), human chorionic gonagotropin-beta (beta-HCG), human growth hormone (HGH), and ferritin, using the C12 diagnostic biochip system. The most relevant tumor markers and the most useful combinations of tumor markers were determined. RESULTS: The overall diagnostic rate for the 130 patients was 42.3%; and the diagnostic rates were 13.6%, 39.5%, 38.2% and 68.8%, for stages I, II, III and IV patients, respectively. There was significant difference in the diagnostic rates between stage I and stage IV patients. Among all the 12 markers, CEA had the highest diagnostic rate of 35.4%. Any combinations of the 5 most relevant tumor markers did not significantly improve the diagnostic rate. However, the combination of 4 markers (CEA+f-PSA +CA125+CA242 or CEA+CA19-9+CA125+f-PSA) was as good as 12 markers in terms of diagnosis. CONCLUSIONS: The C12 biochip diagnostic system has some value in the diagnosis of advanced CRC, but its sensitivity for the diagnosis of early CRC is not satisfactory.

Effects of perioperative cimetidine administration on peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: results of a randomized controlled clinical trial.

BACKGROUND/AIMS: Cimetidine (CIM) seems to have positive effects on the immune systems of cancer patients. This study was conducted to investigate the effects of perioperative administration of CIM on the peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODOLOGY: Forty-nine GI cancer patients were randomized into a treatment group which took CIM in the perioperative period, and a control group which did not take the drug. The treatment was initiated 7 days (d) before operation and continued until 10 d after surgery. At baseline examination, before operation, on the 2nd and the 10th postoperative d, peripheral blood T lymphocytes, helper T cells, T suppressor cells, and NK cells were measured by immunocytochemical method. The surgical specimens were examined for TIL response, and immunohistochemical study was performed to measure the proportion of T and B lymphocytes in the TIL population. RESULTS: In comparison with normal controls, both the treatment and the control groups had decreased T cells, helper T cells and NK cells at baseline. In the control group, total T cells, helper T cells and NK cells declined progressively with the disease course and the decreases became more profound after operation. From the baseline to the 2nd postoperative d, the proportion of total T cells, helper T cells, and NK cells went down from 60.5+/-4.6 to 56.2+/-3.8 percent, from 33.4+/-3.7 to 28.1+/-3.4 percent, and from 15.0+/-2.8 to 14.2+/-2.2 percent, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative d, the treatment group had significantly higher percentages of total T cells, helper T cells and NK cells than control group. Moreover, CIM treatment also boosted the TIL response, as was reflected by findings that 68% (17/25) of the patients in the treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL response. CONCLUSIONS: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity boost TIL responses to tumor.

[Clinical significance of detecting lymph node micrometastasis of colorectal cancer by reverse transcriptase-polymerase chain reaction (RT-PCR)].

BACKGROUND & OBJECTIVE: It remains controversial whether lymph node micrometastasis has impact on staging and prognosis of colorectal cancer. This study was to compare the sensitivity of reverse transcriptase- polymerase chain reaction (RT-PCR) in detecting lymph node micrometastasis of colorectal cancer with pathological morphology and immunohistochemistry, and assess the impact of lymph node micrometastasis on clinical staging and prognosis of colorectal cancer. METHODS: Lymph nodes from 56 cases of colorectal cancer radical resection specimens were studied by RT-PCR to detect the expression of cytokeratin 20 (CK20) mRNA, and compared with routine pathology detection using hematoxylin and eosine (HE) staining, and immunohistochemistry using monoclonal antibody specifically against CK20. The patients had been followed up for 5 years. RESULTS: A total of 432 lymph nodes in 56 patients were analysed by pathological morphology, immunohistochemistry, and RT-PCR, the detected positive lymph node numbers were 247 (57.2%), 269 (62.3%), and 316 (73.1%), respectively. The difference in metastatic lymph node numbers was significant between pathological morphology and RT-PCR method (P< 0.05). Five-year disease- free survival rates of PN0,PN1, and PN2 stages detected by RT-PCR method were 100%, 61.9%, and 55.6%, respectively, significantly higher than those obtained by pathological morphology method, which were 80.0%, 60.0%, and 50.0%, respectively (P< 0.05). CONCLUSIONS: Detecting lymph node micrometastasis of colorectal cancer with RT-PCR method is more sensitive than pathological morphology. RT-PCR method could define the TNM stage and make accurate prognosis for patients with colorectal cancer.

Perioperative cimetidine administration promotes peripheral blood lymphocytes and tumor infiltrating lymphocytes in patients with gastrointestinal cancer: Results of a randomized controlled clinical trial.

AIM: To study the effects of perioperative administration of cimetidine (CIM) on peripheral blood lymphocytes, natural killer (NK) cells and tumor infiltrating lymphocytes (TIL) in patients with gastrointestinal (GI) cancer. METHODS: Forty-nine GI cancer patients were randomized into treatment group, who took CIM in perioperative period, and control group, who did not take the drug. The treatment was initiated 7 days before operation and continued for 10 days after surgery. At baseline examination before operation, on the 2nd and 10th postoperative days, total T lymphocytes, T helper cells, T suppressor cells, and NK cells in peripheral blood were measured respectively by immunocytochemical method using mouse-anti human CD(3), CD(4), CD(8) and CD(57) monoclonal antibodies. Blood samples from 20 healthy volunteers were treated in the same way as normal controls. Surgical specimens were examined during routine histopathological evaluation for the presence of TIL in tumor margin. Immunohistochemical study was performed to measure the proportion of T and B lymphocytes in TIL population. T and B lymphocytes were detected respectively using mouse-anti-human CD(3) and CD(20) monoclonal antibodies. RESULTS: In comparison with normal controls, both the treatment and control groups had decreased T cells, T helper cells and NK cells at baseline. In control group, total T cells, T helper cells and NK cells declined continuously with the disease progression and the decrease became more obvious after operation. From baseline to the 2nd postoperative day, the proportion of total T cells, T helper cells, and NK cells went down from 60.5+/-4.6% to 56.2+/-3.8%, 33.4+/-3.7% to 28.1+/-3.4%, and 15.0+/-2.8% to 14.2+/-2.2%, respectively. On the other hand, there were significant improvements in these parameters after CIM treatment. On the 10th postoperative day, the treatment group had significantly higher percentages of total T cells, T helper cells and NK cells than control group. Moreover, CIM treatment also boosted TIL response, as was reflected by findings that 68% (17/25) of the patients in treatment group had significant TIL responses and only 25% (6/24) of the cases had discernible TIL responses (P<0.01). CONCLUSION: Perioperative application of CIM to GI cancer patients could help restore the diminished cellular immunity induced by tumor burden and surgical maneuver. The drug could also boost TIL responses to tumor. These effects suggest that the drug be used as an immunomodulator for GI cancer patients.