Although considerable progress has been made in understanding how tumors evade immune surveillance, measures to counter the same have not kept pace with the advances made in designing effective strategies. 4-1BB (CD137; TNFRS9), an activation-induced costimulatory molecule, is an important regulator of immune responses. Targeting 4-1BB or its natural ligand 4-1BB ligand (4-1BBL) has important implications in many clinical conditions, including cancer. In-depth analysis revealed that 4-1BB-mediated anti-cancer effects are based on its ability to induce activation of cytotoxic T lymphocytes (CTL), and among others, high amounts of IFN-${\gamma}$. In this review, we will discuss the various aspects of 4-1BB-mediated anti-tumor responses, the basis of such responses, and future directions.
Gastric neuroendocrine tumors (GNETs, also known as gastric carcinoids) are rare form of hormone-secreting neoplasms that present with varied clinical syndromes. There are four types of GNETs based on size, proliferation, localization, differentiation, and hormone production. Type I GNET is related to autoimmune atrophic gastritis and hypergastrinemia. Type II GNETs are related to multiple endocrine neoplasia (MEN)-1, Zollinger-Ellison syndrome and hypergastrinemia. Type 3 GNETs are not associated with any background pathology, and type 4 GNETs are poorly differentiated tumors. The most useful diagnostic and prognostic marker for gastrointestinal NETs is plasma chromogranin A (CgA) levels. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. For optimal management, the type, biology, and stage of the tumor must be considered. Here, we provide a comprehensive and up-to-date review of GNETs.
Cheong, Oh;Joo, Jae Kyun;Park, Young Kyu;Ryu, Seong Yeop;Jeong, Mi Ran;Kim, Ho Koon;Kim, Dong Yi;Kim, Young Jin
Journal of Gastric Cancer
/
v.8
no.3
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pp.129-135
/
2008
Purpose: The usefulness of serum tumor markers for assessing gastric carcinoma is very limited compared to that for neoplasms in other digestive organs. Many reports have shown that serum tumor markers are closely associated with the prognosis and tumor recurrence in gastric cancer patients. However, little is known about the usefulness of serum tumor markers as a predictor of distant metastasis for gastric carcinoma. Materials and Methods: With excluding the non-specific causes of elevated tumor markers, a total of 788 patients with gastric carcinoma and who were seen at our hospitals between 2004 and 2006 were included in this study. The correlation between the preoperative level of tumor makers and the clinicopathological features was analyzed. Results: CEA was significantly correlated with age, gender and nodal metastasis, but not with the depth of tumor. The CEA level was not correlated with distant metastasis, such as peritoneal or hematogenous metastasis. In contrast, the CA 19-9 level was significantly correlated not only with the depth of tumor and nodal metastasis, but also with peritoneal metastasis. Especially, the patients with over 500% elevation of the CA 19-9 level had a significant risk of peritoneal metastasis. Conclusion: CA 19-9 is useful for predicting peritoneal metastasis in gastric cancer patients. It can be used efficiently in making the diagnostic and the treatment plan, in combination with other diagnostic tools, for gastric cancer patients.
Background: We aimed to investigate whether the tumor free distance (the distance between the uterine serosa and the tumor at its deepest point) is useful in surgical staging and in predicting prognosis. Materials and Methods: Data from patients who underwent complete surgical staging for endometrial cancer between January 2006 and June 2011 were reviewed retrospectively. All demographic findings, surgical stages, histological type and grade, myometrial invasion, lymphovascular space invasion as well as abdominal cytology, cervical, adnexal, and omental involvement, and lymph node metastasis were recorded. The relations between myometrial invasion and tumor free distance from uterine serosa with prognostic factors were investigated. Results: Seventy patients were included in the study. Sixty-four (91.5%) had endometrioid type cancers and forty-four (62.9%) were grade 1. The deepest myometrial invasion was less than 1/2 in 42 patients (60%). In 18 patients (25.8%) lymphovascular invasion was noted. Eight (11.4%) were found to have cervical involvement, five (7.1%) had adnexal involvement and in 4 cases (5.7%) the peritoneal washings included malignant cells. Four patients had pelvic and one para-aortic node metastasis. We recognized that an invasion of more than 1/2 was correlated significantly with lymphovascular space involvement, histological grade, positive abdominal washing cytology, nodal and cervical involvement, but not with adnexal involvement. Tumor-free myometrial thickness was negative and statistically significant correlated with surgical stage, histological grade, lymphovascular space involvement, positive abdominal washing cytology, cervical and adnexal involvement. The importance of tumor-free myometrial thickness in determinating the lymphovascular space invasion was found to be highest in terms of sensitivity and specificity when crossing the ROC curve at 11 millimeters. Conclusions: Depth of myometrial invasion is more valuable for predicting lymph node metastasis than tumor-free myometrial thickness. The tumor-free myometrial thickness provides a better prediction for adnexal involvement.
It is necessary to overlap several peaks to form spread out Bragg peak (SOBP) in order to cover the tumor volume because a mono-energetic proton beam forms a narrow Bragg peak. The tumor density has been considered as a brain tissue and then the absorbed dose of the tumor is calculated using Monte Carlo simulations. However, densities of tumors were not a constant. In this study, the SOBP of proton beams was calculated according to changing density of tumors by using Geant4. Tumors were selected as 10 mm and 20 mm width which were the treatment range in the brain phantom. The energies and relative weights of the proton beams were calculated using mathematical formula to form the SOBP suitable for the location and size of the tumor. As the density of the tumor was increased, the 95% modulation range and the practical range were decreased, and average absorbed dose in the 95% modulation range was increased. The change of the tumor density affects the dose distribution of the proton beams, which results in short SOBP within the tumor volume. The consideration of the tumor density affects the determination of the range, so that the margin of the treatment volume can be minimized, and the advantages of proton therapy can be maximized.
Purpose: This study was performed to evaluate the effectiveness of the serum tumor markers CEA, CA 19-9, and CA 72-4 in monitoring the recurrence of gastric cancer and in its preoperative assessment. Materials and Methods: Two hundred fifty-five patients who underwent potentially curative surgery during period from January 1995 to December 2000 at the Department of Surgery were assessed. Serum samples were obtained preoperatively, 2 weeks after the surgery, and at 6-month intervals. The cut-off levels were established as 5 ng/ml for CEA, 36 U/ml for CA 19-9, and 4 U/ml for CA 72-4. The tumor stage was described according to the 5th edition of the Union Internationale Contra la Cancer (UICC) TNM classification in 1997. Results: The preoperative positivities were $10.5\%$ for CEA, $9.7\%$ for CA 19-9, and $12.4\%$ for CA 72-4. The serum levels of the three tumor markers decreased after curative surgery. The preoperative serum levels of the three tumor markers were significantly related to the depth of invasion, the tumor size, lymph-node metastasis, the pathologic stage, and recurrence, except that CEA was not associated with tumor size. The marker sensitivities in recurrent cases were $43.3\%$ for CEA, $\%41.8$ for CA 19-9, and $50.0\%$ for CA 72-4, and the marker specificities were $85.1\%$ for CEA, $96.8\%$ for CA 19-9, and $87.8\%$ for CA 72-4. Conclusion: The preoperative serum levels of CEA, CA 19-9, and CA 72-4 are not useful for the initial diagnosis of gastric cancer because of their low positivity. However, we should consider their relationship with depth of invasion, lymph-node metastasis, tumor size, pathologic stage, and recurrence. Also, the follow-up levels of the three markers have a statistical relationship with recurrence of gastric cancer even though their sensitivities are low.
The Journal of the Korean bone and joint tumor society
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v.17
no.1
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pp.30-35
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2011
Purpose: This study was designed to evaluate the treatment results of malignant melanoma and to analyze the factors influencing prognosis. Materials and Methods: Thirty one cases of malignant melanoma were included in this study. They were treated in our hospital surgically, medically and immunologically from January 1996 to December 2005, and were followed more than 5 years. We compared 5 year survival rate (5YSR) according to the age, gender, anatomical site, depth of tumor, TNM stage, involvement of lymph node and immuno-chemotherapy. Results: Overall 5YSR was 80.6%. 5YSR of the age group below 65 years was 89.7% and 66.7% for the age group over 65 (p=0.033). 5YSR for men was 75% and 90.9% for women. 5YSR according to the site of occurrence showed 66.7% in upper extremities, 89.5% in lower extremities, and 66.7% in other site. 5YSR was 100% for the Clark level below III and 62.5% for the level above IV (p=0.032). 5YSR was 53.8% for lymph node metastasis group and 100% for non-lymph node metastasis group (p=0.021). Conclusion: We concluded that early diagnosis and wide excision was the most important in treatment of malignant melanoma. The prognostic fractors of malignant melanoma were age, depth of tumor (Clark's stage) and metastasis of lymph node.
Purpose: Toxicity of mucosa is one of the major concerns of radiotherapy (RT), when a target tumor is located near a mucosal lined organ. Energy of photon RT is transferred primarily by secondary electrons. If these secondary electrons could be removed in an internal cavity of mucosal lined organ, the mucosa will be spared without compromising the target tumor dose. The purpose of this study was to present a RT dose reduction in near target inner-surface (NTIS) of internal cavity, using Lorentz force of magnetic field. Materials and Methods: Tissue equivalent phantoms, composed with a cylinder shaped internal cavity, and adjacent a target tumor part, were developed. The phantoms were irradiated using 6 MV photon beam, with or without 0.3 T of perpendicular magnetic field. Two experimental models were developed: single beam model (SBM) to analyze central axis dose distributions and multiple beam model (MBM) to simulate a clinical case of prostate cancer with rectum. RT dose of NTIS of internal cavity and target tumor area (TTA) were measured. Results: With magnetic field applied, bending effect of dose distribution was visualized. The depth dose distribution of SBM showed 28.1% dose reduction of NTIS and little difference in dose of TTA with magnetic field. In MBM, cross-sectional dose of NTIS was reduced by 33.1% with magnetic field, while TTA dose were the same, irrespective of magnetic field. Conclusion: RT dose of mucosal lined organ, located near treatment target, could be modulated by perpendicular magnetic field.
Purpose: Among cell adhesion molecules, serum levels of intercellular adhesion molecule-1 and E-selectin are known to be correlated with the metastatic potential of gastric cancer. In the present study, the authors investigated the expression of intercellular adhesion molecule-1 and E-selectin in gastric cancer tissues and cultured gastric cancer cells, and examined their clinical value in gastric cancer. Materials and Methods: The protein was extracted from gastric cancer tissues and cultured gastric cancer cells (MKN-28 and Kato-III) and the expression of intercellular adhesion molecule-1 and E-selectin was examined by western blotting. The clinical significance of intercellular adhesion molecule-1 and E-selectin was explored, using immunohistochemical staining of specimens from 157 gastric cancer patients. Results: In western blot analysis, the expressions of intercellular adhesion molecule-1 in gastric cancer tissues and cultured gastric cancer cells were increased, however, E-selectin in gastric cancer tissues and cells were not increased. Among 157 gastric cancer patients, 79 patients (50%) were intercellular adhesion molecule-1 positive and had larger tumor size, an increased depth of tumor invasion, lymph node metastasis and perineural invasion. The intercellular adhesion molecule-1 positive group showed a higher incidence of tumor recurrence (40.5%), and a poorer 3-year survival than the negative group (54.9 vs. 85.9%, respectively). Conclusions: Intercellular adhesion molecule-1 is overexpressed in gastric cancer tissues and cultured gastric cancer cells, whereas E-selectin is not overexpressed. Increased expression of intercellular adhesion molecule-1 in gastric cancer could be related to the aggressive nature of the tumor, and has a poor prognostic effect on gastric cancer.
The use of therapeutic ultrasound(US) in humans with malignant neoplasms has been contraindicated in physical therapy practice. Some studies have shown that results after application of US differ according to tumor type and penetration depth. The purposes of this study were to determine the effects of US on melanoma in mice and to determine treatment dosage. Twenty-four female C57BL/6 mice, age 8 weeks. The right flank of all mice was shaved, and a 0.1 ml suspension of cells was injected subcutaneously into the animals' right flank. In this study, 24 subjects were randomly divided into three groups: experimental group 1(n=8), experimental group 2(n=8), control group(n=8). In the experimental group 1, animals received continuous 3 MHZ US treatment, administered at $2.0W/cm^2$ for five minutes. In experimental group 2, animals received continuous 3 MHz US treatment, administered at $1.0W/cm^2$ for 5 minutes. The control group received the same handling as other experimental groups, including rodent chow, water, US gel application but US head pressure without the power turned on. After 10 days treatment, all mice were killed with a potassium solution. Tumors were excised and weighed on an electrical balance and fixed in a 10% neutral buffered formalin solution. Tumor weights were smaller in experimental group 2(0.3838 g) than in the control group(0.6275 g). Tumor weights of the experimental group 1(0.015 g) were smaller than those of experimental group 2. Continuous therapeutic US decreased the weight of subcutaneous melanoma tumors in mice. The treatment dosage($2.0W/cm^2$) we suggest was more effective than earlier studies on decreasing tumor size with ultrasound.
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