• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.9611-9614
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• 2014

Purpose: To investigate the clinical value in lung cancer of a combination of four serum tumor markers, haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Materials and Methods: Serum Hp (with immune-turbidimetric method), CEA, NSE, CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patients with benign lung disease and 150 healthy controls. Differences of expression were compared among groups, and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed. Results: Serum tumor marker levels in patients with lung cancer were obviously higher than those with benign lung disease and normal controls (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%, with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce a positive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, the positive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinoma case, the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, the positive detection rate of NSE was highest. The area under receiver operating characteristic curve ($AUC^{ROC}$) of Hp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665). Conclusions: Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be useful for pathological typing.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7831-7834
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• 2014

Objective: To explore the influence of different ways of blood transfusion on the expression levels of interleukins (IL) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) inperi-operative patients with esophageal cancer. Materials and Methods: A total of 80 patients with esophageal cancer who underwent radical operations were selected as study patients and randomly divided into an observation group (treated with autologous blood transfusion) and control group (with homologous blood transfusion). Changes of intra-operative indexes and peri-operative blood indexes, from hemoglobin (Hb) and hematocrit value (Hct), to levels of inflammatory factors like interleukins-6 (IL-6), IL-8, IL-10 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) were compared. Results: Operations for patients in both groups were successfully conducted, and no significant differences in mean surgical duration and intra-operative hemorrhage volume, fluid infusion volume and blood transfusion volume were detected (p>0.05). Compared with values before surgery, Hb and Hct levels decreased significantly while white blood cell count (WBC) increased 1, 5 and 7 d after operation (p<0.05, p<0.01). In addition, WBC was apparently higher in observation group than in control group 5 and 7 d after operation (p<0.01). Compared with before surgery, in the observation group, levels of IL-6, IL-8 and IL-10 had no significant differences after operation (P>0.05), but TNF-${\alpha}$ level increased y (p<0.01), whereas in control group, IL-6 level had no significant difference (p>0.05), IL-8 level decreased obviously (p<0.05), IL-10 level increased markedly first and then decreased gradually as time passed but its level remained elevated (p<0.01), and TNF-${\alpha}$ level increased first and then decreased, and there was no significant difference 7 d after operation (p>0.05). Conclusions: Decreased IL-8 and increased IL-10 levels are two important reasons for immunosuppression after homologous blood transfusion, whereas autologous blood transfusion can alleviate this while increasing the TNF-${\alpha}$ level, which also has potential to improve anti-tumor immunity in the human body.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4825-4832
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• 2015

Incidence rates of nasopharyngeal carcinoma are high in Indonesia, Singapore and South-Eastern China. Chemoradiotherapy has been the standard regimen for locally advanced nasopharyngeal carcinoma according to guidelines from the National Comprehensive Cancer Network. Recently, advances in the management of nasopharyngeal carcinoma have transferred into better treatment outcomes. Most phase III clinical trials support the addition of concurrent chemotherapy to radiotherapy for the initial treatment of these patients. Studies evaluating effects and toxicity of concurrent chemotherapy with different regimens have been reported. However, the status of adding adjuvant chemotherapy or induction chemotherapy remains controversial. Recent studies have shown that adjuvant chemotherapy with two or three cycles may improve survival for nasopharyngeal carcinoma with stage N2-3 disease or with persistently detectable plasma EBV DNA after radiotherapy. This review examines the pertinent issues and latest studies concerning the management of loco-regionally advanced NPC, regarding concurrent chemotherapy, adjuvant chemotherapy, and induction chemotherapy in decades.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4891-4894
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• 2015

Background: To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of nonsmall cell lung cancer (NSCLC). Materials and Methods: Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. Results: Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (P<0.05). The sensitivity of CEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA + CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (P<0.05) and elevation of serum CEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (P<0.05). Conclusions: Single measurement of CEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA + CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5731-5734
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• 2013

Background: The object of this study was to examine whether a new protocol including step-sectioning and immunohistochemistry (IHC) staining of axillary sentinel nodes (SN) would lead to detection of more metastases in patients with breast cancer. Materials and Methods: Sixty-nine tumor free sentinel lymph nodes were examined. Step frozen sectioning was performed on formalin fixed SN and stained both by hematoxylin and eosin (H and E) and cytokeratin markers using IHC. Any tumoral cell in IHC stained slides were considered as a positive result. Metastases up to 0.2 mm were considered as isolated tumor cells and 0.2 up to 2 mm as micrometastasis. Results: Mean age of the patients was $48.7{\pm}12.2$ years. Step sectioning of the SN revealed 11 involved by metastasis which was statistically significant (p<0.001). Furthermore, 15 (21.7%) of the patients revealed positive results in IHC staining for pan-CK marker and this was also statistically significant (p=0.001). Ten patients had tumoral involvement in lymph nodes harvested from axillary dissection and 4 out of 15 lymph nodes with positive result for CK marker were isolated tumor cells. However, 4 of 10 patients with tumor positive lymph nodes in axillary dissection were negative for CK marker and in contrast 6 of the pan-CK positive SN were in patients with tumor-free axillary lymph nodes. Conclusions: Both IHC and step sectioning improve the detection rate of metastases. Considering the similar power of these two methods, we recommend using either IHC staining or step sectioning for better evaluation of harvested SNs.

• BMB Reports
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• v.52 no.3
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• pp.214-219
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• 2019

The role of tumor-proximal factors in tumor plasticity during chemoresistance and metastasis following chemotherapy is well studied. However, the role of endothelial cell (EC) derived paracrine factors in tumor plasticity, their effect on chemotherapeutic outcome, and the mechanism by which these paracrine factors modulate the tumor microenvironment are not well understood. In this study, we report a novel mechanism by which endothelial miR-125a and let-7e-mediated regulation of interleukin-6 (IL-6) signaling can manipulate vasculogenic mimicry (VM) formation of MDA-MB-231 breast cancer cells. We found that endothelial IL-6 levels were significantly higher in response to cisplatin treatment, whereas levels of IL-6 upon cisplatin exposure remained unchanged in MDA-MB-231 breast cancer cells. We additionally found an inverse correlation between IL-6 and miR-125a/let-7e expression levels in cisplatin treated ECs. Interestingly, IL-6, IL-6 receptor (IL-6R), and signal transducer and activator of transcription 3 (STAT3) genes in the IL-6 pathway are closely regulated by miR-125a and let-7e, which directly target its 3' untranslated region. Functional analyses revealed that endothelial miR-125a and let-7e inhibit IL-6-induced adhesion of monocytes to ECs. Furthermore, conditioned medium from cisplatin treated ECs induced a significantly higher formation of VM in MDA-MB-231 breast cancer cells as compared to that from intact ECs; this effect of cisplatin treatment was abrogated by concurrent overexpression of miR-125a and let-7e. Overall, this study reveals a novel EC-tumor cell crosstalk mediated by the endothelial miR-125a/let-7e-IL-6 signaling axis, which might improve chemosensitivity and provide potential therapeutic targets for the treatment of cancer.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.387-396
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• 2022

Skeletal muscle accounts for about 40-50% of body weight and is an important tissue that performs various functions, such as maintaining posture, supporting soft tissues, maintaining body temperature, and respiration. Cancer, which occurs widely around the world, causes cancer cachexia accompanied by muscular atrophy, which reduces the effectiveness of anticancer drugs and greatly reduces the quality of life and survival rate of cancer patients. Therefore, research to improve cancer cachexia is ongoing. However, there are few studies on the link between cancer and muscle atrophy. Cancer cells exhibit distinct microenvironment and metabolism from tumor cells, including tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), and insulin resistance due to the Warburg effect. Therefore, we summarize the microenvironment and metabolic characteristics of cancer cells, and the molecular mechanisms of muscle atrophy that can be affected by cytokine and insulin resistance. In addition, this suggests the possibility of improving cancer cachexia of substances affecting TAM, TAN, and Warburg effect. We also summarize the mechanisms identified so far through single agents and the signaling pathways mediated by them that may ameliorate cancer cachexia.

• The Journal of Internal Korean Medicine
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• v.45 no.3
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• pp.508-518
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• 2024

Objectives: To report a correlation of IL-6 of pancreatic cancer and cancer progression in three pancreatic cancer patients. Method: Three pancreatic cancer patients were monitored for changes in IL-6 levels, tumor markers (CEA, CA19-9), and clinical outcomes over their treatment period. Results: Patient 1's IL-6 levels rose with liver metastasis and tumor progression, coinciding with increases in tumor markers. Patient 2's IL-6 levels remained elevated during chemotherapy, correlating with tumor growth. Patient 3's IL-6 levels spiked prior to cancer progression. Conclusion: Elevated IL-6 levels were observed in advancing pancreatic cancer patients, suggesting IL-6 as a potential biomarker for monitoring cancer progression in pancreatic cancer. Regular IL-6 monitoring could improve prognostic evaluations and treatment strategies.

• Radiation Oncology Journal
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• v.9 no.1
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• pp.7-15
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• 1991

Pentoxifylline (PENTO) has been known to improve RBC fluidity, and thus improve the flux of RBC through narrow capillaries. Additionally, PENTO also decreases the $O_2$ affinity of hemoglobin by increasing 2,3-DPG levels, thereby increasing the $O_2$ release from RBC. Nicotinamide (NA) has been reported to decrease the number of acutely hypoxic cells in tumors by temporarily increasing tumor blood flow. Therefore, the purpose of this study was to examine whether the combination of PENTO and NA (PENTO+NA) would reduce the radioresistance of the Fsall murine fibrosarcoma by oxygenating the hypoxic cells. We obsewed a significantly enhanced radiation-induced growth delay of the FSaII tumors by PENTO+NA. Thus the enhancement ratio was between 2.5 and 2.8 in growth delay assay. The $TCD_{50}$ of control tumors was about 57 Gy, but that of PENTO+NA treated tumors was about 32Gy. Thus $TCD_{50}$ was modified by a factor of 1.8. We also observed that PENTO+NA exerted no effect on the radiation-induced skin damage after the legs without bearing tumors were exposed to X-irradiation. In order to clarify radiosensitizing effects of PENTO+ NA, changes in tumor blood flow and intratumor pOf were measured using laser Doppler flowmetry and $O_2$ microelectrode methods. The tumor blood flow significantly increased at 10 min. after injection of PENTO+ NA. Furthermore, we also found that PENTO+ NA significantly increased intratumor $pO_2$ from 8 to 19 mmHg. We concluded that PENTO+MA was far more effective than NA alone or PENTO alone. The increase in the response of tumors in vivo to X-irradiation appeared to be due mainly to an increase in the tumor oxygenation. Further studies using various concentrations of PENTO alone and in combination with NA to obtain better sequencing and maximal radiosensitization are warranted.

• Journal of Electrodiagnosis and Neuromuscular Diseases
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• v.20 no.2
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• pp.98-105
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• 2018

Objective: To evaluate whether the increase of the amplitude of motor evoked potentials (MEPs) during surgery can imply favorable prognosis postoperatively in spinal cord tumor surgery. Method: MEPs were monitored in patients who underwent spinal cord tumor surgery between March 2016 and March 2018. Amplitude changes at the end of monitoring compared to the baselines in limb muscle were analyzed. Minimum and maximum changes were set to $MEP_{min}$ (%) and $MEP_{max}$ (%). Strengths of bilateral 10 key muscles which were documented a day before ($Motor_{pre}$), 48 h ($Motor_{48h}$) and 4 weeks ($Motor_{4wk}$) after the surgery were reviewed. Results: Difference of $Motor_{48h}$ from $Motor_{pre}$ ($Motor_{48h-pre}$) and $Motor_{4wk}$ from $Motor_{pre}$ ($Motor_{4wk-pre}$) positively correlated with $MEP_{min}$, suggesting that smaller the difference of MEPs amplitude, less recovery of muscle strength. There was a negative correlation between the amount of bleeding and $MEP_{min}$, indicating that the greater the amount of bleeding, the smaller the $MEP_{min}$, implying that MEPs amplitude is less likely to improve when the amount of bleeding is large. It also showed significant difference between patients with improved or no change of motor status and patients with motor deterioration after surgery according to anatomical tumor types. Conclusion: Improve of muscle strength was less when the increase of MEPs amplitude was small, and improvement of MEPs amplitude was less when the amount of bleeding was large. Correlation between changes of status of muscle strength after surgery and tumor types was observed. With amplitude increase in MEPs monitoring, restoration of muscle strength can be expected.