Outcomes in elderly patients treated with a single-agent or combination regimen as first-line chemotherapy for recurrent or metastatic gastric cancer.

BACKGROUND: Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients. METHODS: Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated. RESULTS: Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71-89) in the single regimen group (SG, 70 patients) and 73 years (range 71-81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85-5.95) and 4.1 months (95 % CI 2.62-5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17-9.08) and 7.6 months (95 % CI 5.50-9.69; P = 0.782), respectively. Hematologic (P < 0.001) and non-hematologic toxicities (P < 0.001) were more frequent in the CG. The most common causes of chemotherapy cessation were disease progression in the SG and decreased performance status in the CG. CONCLUSIONS: Single-agent treatment should be considered a first-line palliative chemotherapy option for elderly patients with GC.

Human papillomavirus-stratified analysis of the prognostic role of miR-21 in oral cavity and oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) infection plays a significant role in the development and progression of head and neck squamous cell carcinoma (HNSCC). Expression of miR-21 has a prognostic role in a wide variety of cancers. The upregulation of miR-21 suppresses a number of target genes, including phosphatase tensin homologue (PTEN) and programmed cell death 4 (PDCD4). We investigated the association between the expression of miR-21 and the clinical features of HNSCC using stratified analysis based on HPV infection status. HPV status and miR-21 expression in HNSCC tissues from 167 patients were evaluated using in situ hybridization. The expression of PDCD4 and PTEN was examined by immunohistochemistry. The up-regulation of stromal miR-21 expression occurred in 40.6% of HPV-negative samples and 28.3% of the HPV-positive group. In HPV-stratified multivariate analysis, high miR-21 expression was associated with poor cancer-specific survival in HPV-negative tumors, but not in HPV-positive tumors. There was a significant association between miR-21 and cytoplasmic PDCD4 overexpression in HPV-negative HNSCCs. We suggest that stromal miR-21 expression is an independent prognostic factor in HPV-negative tumors and miR-21 may play different roles depending on HPV infection status.

Prognostic significance of TMEM16A, PPFIA1, and FADD expression in invasive ductal carcinoma of the breast.

BACKGROUND: 11q13 region is a frequently amplified locus in human malignancies. Among the genes located in this region, FADD is one of the alleged driving genes. Because amplification is not generally confined to a single gene and amplified genes may not show increased expression, we need to evaluate clinical significance of changes occurring in 11q13 region to understand their roles in carcinogenesis. Therefore, we screened expressions of FADD and closely located genes (PPFIA1 and TMEM16A) and evaluated the expressions to find clinical significance in invasive ductal carcinoma of the breast. METHODS: Ninety-eight cases of invasive ductal carcinoma of the breast were collected. Using archival tissues resected from the cases, we built a tissue microarray and used it in immunohistochemistry. We evaluated the association of FADD, PPFIA1, and TMEM16A expression scores with clinicopathological parameters, including disease-free survival. RESULTS: FADD expression was associated with T stage (P=0.046). The combined score of FADD, PPFIA1, and TMEM16A gene expressions was associated with perineural invasion (P=0.022). Although individual gene expressions of TMEM16A, FADD, and PPFIA1 failed to show significant association with disease-free survival, combined gene expression scores did show association with disease-free survival (P=0.034). CONCLUSIONS: FADD, TMEM16A, and PPFIA1 gene expressions as a whole were associated with disease-free survival in breast cancer.

Soluble interleukin-6 receptor is a prognostic marker for relapse-free survival in estrogen receptor-positive breast cancer.

Considering the protumorigenic roles of interleukin-6 (IL-6) transsignaling, we assessed the serum levels of IL-6, soluble interleukin-6 receptor (sIL-6R), and soluble glycoprotein 130 (sgp130) in 143 patients with breast cancer. Serum levels of IL-6 were elevated with advanced T and N stage. Serum levels of sIL-6R were lower in patients with estrogen receptor-positive cancer. The median values of IL-6 and sgp130 did not differ between patients with recurrence and those without recurrence. However, higher serum levels of sIL-6R at diagnosis were associated with significantly shorter relapse-free survival in patients with estrogen receptor-positive breast cancer.

Treatment outcomes of systemic chemotherapy for peritoneal carcinomatosis arising from gastric cancer with no measurable disease: retrospective analysis from a single center.

BACKGROUND: Few studies of systemic chemotherapy have focused on gastric cancer with peritoneal carcinomatosis (PC) without measurable lesions. In the present study, we characterized the outcomes of systemic chemotherapy and prognostic factors for gastric cancer with PC, particularly in patients without measurable disease. METHODS: Clinical data from 211 gastric cancer patients with PC (137 without and 74 with measurable disease) who had received systemic chemotherapy between January 2003 and December 2010 at a single center were reviewed. RESULTS: The median overall survival (OS) rate of gastric cancer patients with PC with no measurable disease was significantly longer than that of patients with measurable disease (18.0 vs. 11.6 months, p = 0.010). On multivariate analysis, poor performance status [hazard ratio (HR) = 2.15, p < 0.001], the presence of metastatic lymphadenopathy (HR = 2.17, p < 0.001), and high-grade PC (HR = 1.83, p = 0.001) were associated with significantly decreased OS. When patients with low-grade PC were stratified by clinical PC grade, the median OS of those without measurable disease was 19.6 months. The median OS of patients with low-grade PC with no measurable disease was longer than those of patients with high-grade PC without measurable disease, patients with low-grade PC with measurable disease, and patients with high-grade PC with measurable disease (p = 0.001, p = 0.029, and p < 0.001, respectively). Among the patients with low-grade PC, patients who received a gastrectomy had longer survival than patients who did not receive a gastrectomy (p < 0.001). CONCLUSIONS: In our study, clinically low-grade PC without measurable disease was associated with better outcomes of systemic chemotherapy than the outcomes in the other groups examined. Clinical trials in patients with gastric cancer with PC should be stratified according to PC grade.

Prognostic significance of RSPO1, WNT1, P16, WT1, and SDC1 expressions in invasive ductal carcinoma of the breast.

BACKGROUND: To better understand the mechanisms of the SDC1 expression in invasive ductal carcinoma, we studied the correlations between SDC1 expression and related gene expressions (RSPO1, WNT1, WT1, and P16). METHODS: Using 100 cases of invasive ductal carcinoma tissue, we screened expressions of RSPO1, WNT1, WT1, P16, and SDC1 using immunohistochemistry. We analyzed the association between the immunoreactivities and clinicopathological parameters. RESULTS: WT1 expression was associated with tumor grade. RSPO1 expression was associated with progesterone receptor expression. Expressions of RSPO1, WT1, and P16 were significantly associated with disease-free survival. RSPO1 and P16 showed statistically significant hazard ratios. SDC1 ectodomain expression was significantly associated only with P16 expression. Immunoreactivity of SDC1 cytoplasmic domain was associated with WT1 and WNT1. However, WNT1 expression failed to show a significant association with disease-free survival. CONCLUSIONS: RSPO1 and P16 immunoreactivity was found to be an independent prognostic indicator in invasive ductal cancer. Cytoplasmic expression of SDC1 is positively correlated with tumor-prone proteins (WT1 and WNT1) and membranous expression of SDC1 is positively correlated with the tumor suppressor (P16).

Photoconductivity and enhanced memory effects in hybrid C60-graphene transistors.

We describe the observation of photoconductivity and enhanced memory effects in graphene devices functionalized with clusters of alkylated C(60) molecules. The alkylated C(60) clusters were adsorbed on chemical vapor deposition-grown graphene devices from an aprotic medium. The resulting alkylated C(60)-graphene hybrid devices showed reproducible photoconductive behavior originating from the electron-accepting nature of the C(60) molecules. Significantly enhanced gate hysteresis was observed upon illumination with visible light, thereby enabling the use of C(60)-graphene hybrid devices in three-terminal photo-memory applications.

Effect of green tea extracts on oxaliplatin-induced peripheral neuropathy in rats.

BACKGROUND: A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin. METHODS: We conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models. RESULTS: A total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group. CONCLUSIONS: Green tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.

Prognostic significance of CD44s expression in resected non-small cell lung cancer.

BACKGROUND: CD44s is a cell adhesion molecule known to mediate cellular adhesion to the extracellular matrix, a prerequisite for tumor cell migration. CD44s plays an important role in invasion and metastasis of various cancers. In the present study, we sought to determine whether CD44s is involved in clinical outcomes of patients with resected non-small cell lung cancer (NSCLC). METHODS: Using immunohistochemical staining, we investigated CD44s protein expression using tissue array specimens from 159 patients with resected NSCLC (adenocarcinoma (AC; n=82) and squamous cell carcinoma (SCC; n=77). Additionally, the immunoreactivity of cyclooxygenase (COX)-2 was also studied. The clinicopathological implications of these molecules were analyzed statistically. RESULTS: High CD44s expression was detected more frequently in NSCLC patients with SCC (66/72; 91.7%) than in those with AC histology (P<0.001). Additionally, high CD44s expression was significant correlated with more advanced regional lymph node metastasis (P=0.021). In multivariate analysis of survival in NSCLC patients with AC histology, significant predictors were lymph node metastasis status (P<0.001), high-grade tumor differentiation (P=0.046), and high CD44s expression (P=0.014). For NSCLC patients with SCC histology, the significant predictor was a more advanced tumor stage (P=0.015). No significant association was found between CD44s and clinical outcome (P=0.311). CONCLUSIONS: High CD44s expression was a negative prognostic marker with significance in patients with resected NSCLC, particularly those with AC histology, and was independent of tumor stage.

Pancreatic endocrine tumors: a report on a patient treated with sorafenib.

A 31-yr-old man with abdominal pain was diagnosed with a pancreatic endocrine tumor and multiple hepatic metastases. Despite optimal treatment with interferon alpha, a somatostatin analog, local therapy with high-intensity focused ultrasound ablation for multiple hepatic metastases, and multiple lines of chemotherapy with etoposide/cisplatin combination chemotherapy and gemcitabine monotherapy, the tumor progressed. As few chemotherapeutic options were available for him, sorafenib (800 mg/day, daily) was administered as a salvage regimen. Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed tumor progression compared to the previous immunotherapy and chemotherapy. Serial computed tomography scans showed that the primary and metastatic tumors were stable. Thirteen months after beginning targeted therapy, and up to the time of this report, the patient is well without disease progression. We suggest that sorafenib is effective against pancreatic endocrine tumors.

Resolving microscopic interfaces in Si(1-x)Ge(x) alloy nanowire devices.

We have fabricated Si(1-x)Ge(x) alloy nanowire devices with Ni and Ni/Au electrodes. The electrical transport characteristics of the alloy nanowires depended strongly on the annealing temperature and contact metals. Ni/Au-contacted devices annealed at 400 degrees C showed p-type transistor behavior as well as a resistance switching effect, while no switching was observed from Ni-contacted alloy nanowire devices. To identify the origin of such a hysteretic resistance switching effect, we constructed nanowire devices on a 40 nm Si(3)N(4) membrane. Transmission electron microscopy analysis combined with electrical transport measurements revealed that devices contacted with Ni/Au, and thereby showing resistance switching, have Au atoms right next to the alloy nanowire.

Aptamers as molecular recognition elements for electrical nanobiosensors.

Recent advances in nanotechnology have enabled the development of nanoscale sensors that outperform conventional biosensors. This review summarizes the nanoscale biosensors that use aptamers as molecular recognition elements. The advantages of aptamers over antibodies as sensors are highlighted. These advantages are especially apparent with electrical sensors such as electrochemical sensors or those using field-effect transistors.

The modification of the electrical property in double-walled carbon nanotube devices with a self-assembled monolayer of molecules.

We have investigated the electrical transports of double-walled carbon nanotube field effect transistors (DWNT-FETs) with modified contacts. The CNT/Au metal contacts of DWNT-FETs were modified with a self-assembled monolayer of 2-aminoethanethiol molecules. In ambient air, the contact-modified DWNT-FETs showed a decreased conductance in the p-channel (negative gate voltages) and an increased conductance in the n-channel (positive gate voltages), while the original device showed p-type transport. In a vacuum, the n-channel current in the contact-modified DWNT-FET started to rise. We observed a clear n-type transport in the high vacuum. Almost no changes in the gate threshold voltages were observed by means of the contact-modification with a self-assembled monolayer. While the semiconducting DWNT-FET showed a clear transition from a p-type to n-type transistor with contact modification, no apparent changes were observed in semi-metallic DWNT devices.

First reported case of interferon-alpha-induced sarcoidosis in an Asian patient with malignant melanoma.

Anticancer agents can induce sarcoidosis. Interferon-alpha, which is used for the treatment of malignant melanoma and renal cell cancer, is one causative agent of sarcoidosis. However, there are few reports of interferon-alpha-induced sarcoidosis in patients with malignant melanoma. Clinically, it is important to consider the possibility of sarcoidosis in such patients because it could be easily regarded as a metastatic lesion due to underlying malignancy and given unnecessary treatment. Here, we report on the first case of interferon-alpha-induced sarcoidosis in an Asian melanoma patient.

Clinical outcome of induction chemotherapy in locally advanced head and neck squamous cell carcinoma.

UNLABELLED: BACKGROUND AIM: We evaluated the efficacy and toxicities of three induction chemotherapy regimens in locally advanced head and neck cancer and assessed the clinical significance of human papillomavirus (HPV) in induction chemotherapy. PATIENTS AND METHODS: Fifty-two patients were retrospectively evaluated; 12 patients received 5-fluorouracil-plus-cisplatin (FP); 24 patients received docetaxel-plus-cisplatin (DP); 16 patients received docetaxel, cisplatin, and 5-fluorouracil (TPF). RESULTS: The TPF regimen showed a trend towards a higher overall response rate and pathological complete response and led to a significantly higher rate of metabolic complete response. Patients with HPV-positive tumors exhibited a significantly higher pathological complete response rate than those with HPV-negative tumors. In univariate analysis, the prognostic factors significantly affecting progression-free survival were lymph node stage, and metabolic and pathological complete response. CONCLUSION: TPF induction chemotherapy tended to improve clinical outcome, with manageable toxicity. Pathological complete response was positively correlated with HPV positivity.

Serum Carcinoembryonic Antigen Levels and the Risk of Whole-body Metastatic Potential in Advanced Non-small Cell Lung Cancer.

BACKGROUND: This study aimed to clarify the clinical associations between serum carcinoembryonic antigen (CEA) levels and whole-body metastatic distribution in stage IV NSCLC patients. METHODS: This study analyzed 377 eligible patients between June 2007 and December 2012. All patients enrolled in the study were newly diagnosed with stage IV NSCLC and had records of pre-treatment serum CEA levels. The serum CEA levels were categorized as normal (< 5 ng/ml) or abnormal (≥ 5 ng/ml) to reveal clinically correlated factors with abnormal serum CEA levels. RESULTS: The median age of the study cohort was 65 years old (range, 30-94), and 236 (62.6%) patients were male. Two hundred seventy-seven (73.5%) patients had tumors with a histology that is consistent with adenocarcinoma. The median serum CEA value was 8.2 ng/ml (range, 0.1-2872.7), and 218 (57.8%) patients had abnormal serum CEA levels. In multivariate analysis, abnormal serum CEA levels had statistically strong associations with non-squamous cell histology (P=0.002), bone (P=0.001), and brain metastases (P=0.005); and were also closely correlated with positive metastatic LN status (P=0.083) and pulmonary metastasis (P=0.065). Very high serum CEA levels (≥ 100 ng/ml) were additionally correlated with abdominal/pelvic metastasis (P < 0.001). CONCLUSIONS: Our findings suggested that abnormal serum CEA levels were strongly correlated with increased whole-body metastatic potential in advanced NSCLC. The results provided evidence for future exploratory anti-CEA targeting and intensive systemic assessment in advanced NSCLC patients with abnormal serum CEA levels.

Prognostic significance of autophagy-related protein expression in resected pancreatic ductal adenocarcinoma.

OBJECTIVES: Autophagy is a critical intracellular pathway for the removal of aggregated proteins and damaged organelles. The aim of this study was to explore the contribution of autophagy-related proteins to clinical outcomes of patients with resected pancreatic ductal adenocarcinoma (PDAC). METHODS: The expression of 5 autophagy-related proteins in the PDAC tissues of 73 patients was evaluated by immunohistochemistry using a tissue array method. In addition, clinicopathological characteristics and survival were compared with the expression of autophagy-related proteins. RESULTS: Of the 73 patients, autophagy-related protein expression frequencies were 49.3% (36/73) for Atg5, 63.9% (46/72) for Ambra1, 47.9% (35/73) for beclin-1, 83.3% (60/72) for LC3B, and 69.9% (51/73) for Bif-1. The correlation between the expressions of autophagy-related proteins was significant for all protein pairs. Advanced T stage was marginally associated with a higher number of protein changes (P = 0.059). Multivariate analysis revealed that beclin-1 overexpression and increases in the alteration of autophagy-related proteins were independently associated with poor prognosis (hazard ratio of 5.365, P = 0.001 and hazard ratio of 5.270, P = 0.022, respectively). CONCLUSIONS: The acquisition of autophagy-related proteins is associated with poor clinical outcome in PDAC. The detection and inhibition of autophagy offers a potential therapeutic target for PDAC.

Comparison of the efficacy and the toxicity between gemcitabine with capecitabine (GC) and gemcitabine with erlotinib (GE) in unresectable pancreatic cancer.

OBJECTIVE: We retrospectively compared the efficacy and toxicity of gemcitabine combination with capecitabine or erlotinib in unresectable pancreatic cancer to know whether the combination with cytotoxic and target agent has more benefit comparing to combination of cytotoxic agents. METHODS: Fifty-three patients with unresectable pancreatic cancer, treated with gemcitabine and capecitabine (GC) or gemcitabine and erlotinib (GE) as first line between October 2006 and July 2010, were reviewed. In GC group, patients were treated with gemcitabine 1,000 mg/m(2) on days 1, 8, and capecitabine 1,300 mg/m(2) bid was administered on days 1-14, repeated every 21 days. In GE group, gemcitabine was given at 1,000 mg/m(2) I.V for 30 min on days 1,8,15, and erlotinib was taken orally at 100 mg through days 1-28, repeated every 28 days. RESULTS: Response rate was similar, 23.5 % in GE and 21.1 % in GC, but GC had better disease control rate with 73.7 % than GE with 52.9 %. GC also showed longer PFS and OS (5.37 and 14.43 months) than GE (2.63 and 6.23 months) (p = 0.032 for PFS and 0.002 for OS). In toxicity profiles, GC had more hematologic toxicities and GE had more non-hematologic toxicities. CONCLUSIONS: The combination with cytotoxic agents seems to have better efficacy and clinical outcome than combination with cytotoxic agent and target agent. The new combination should be developed for the treatment for advanced pancreatic cancer.

IL-6 is an independent risk factor for resistance to erythropoiesis-stimulating agents in hemodialysis patients without iron deficiency.

Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.