Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advanced breast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials and consequently are widely used. In this study aimed to research the complete response (pCR) rates in different regimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This study included 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvant chemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response to neoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumor in the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesterone receptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor was defined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumor ER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14 (min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal. Staging was performed postoperatively based on the pathology report and appropriated imaging modalities The TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven (90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade II and 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. The patients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response to chemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 and doxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40 patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17 patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCR was higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the group that treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Some other factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentage of ER positivity, and HER2 expression.
Norovirus is the most common cause of acute gastroenteritis. Its pathogenesis is poorly understood owing to the difficulty of establishing viral infection in animal models. Here, post-weaning gnotobiotic pigs were infected with human norovirus genogroup II genotype 4 (HuNoV GII.4) to investigate the pathogenesis and replication of the virus. Three groups of four pigs were infected with $1{\times}10^5$, $1{\times}10^6$, or $1{\times}10^7$ genomic equivalent (GE) copies of HuNoV GII.4. Four pigs were used as negative controls. Blood and rectal swab samples were collected after viral infection, and gross legions were examined after necropsy. Diarrhea was induced in 25% and 75% of pigs infected with $1{\times}10^6$ and $1{\times}10^7$ GE copies, respectively. Viral shedding was detected in 50%, 75%, and 50% of pigs infected with $1{\times}10^5$, $1{\times}10^6$, and $1{\times}10^7$ GE copies, respectively. Viremia was detected in 25% of pigs infected with either $1{\times}10^6$ or $1{\times}10^7$ GE copies. When gross lesions of gastroenteritis were investigated, the ileum walls of the infected pigs were thinner than those of the controls. Villi atrophy and inflammatory cell infiltration were identified in the ileum of each infected pig. Viral capsid was identified in the jejunum, ileum, colon, spleen, and mesenteric lymph node. Virus replication was newly verified in the spleen and mesenteric lymph nodes by detection of negative-sense viral RNA. In conclusion, HuNoV GII.4 could induce acute gastroenteritis and replicate in the extra-intestinal lymphoid tissues in post-weaning gnotobiotic pigs. Therefore, such pigs would be a suitable animal model for studying the pathogenesis and replication of HuNoV.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
/
v.27
no.4
/
pp.289-300
/
2001
Telomerase is a ribonucleoprotein that synthesizes telomere repeats. It has been reported that activation of telomerase was associtated with immortalization, proliferative activity and carcinogenesis. Recently, telomerase activity has been extensively studied in many kinds of malignant tumors for clinical diagnostic and/or prognostic utilities. In neuroblastoma, breast carcinoma, gastric carcinoma, non-small cell lung carcinoma, close relationship has been reported between high telomerase activity and lymph node metastasis, tumor aggressiveness and poor prognosis. The purpose of this study is to investigate the clinical implication of telomerase activity assay as an adjunctive factor in decision-making on neck node management, speedy pre-operative judging on histologic malignancy grading. Thus we performed semi-quantitative assay of telomerase activity using Telomerase PCR ELISA $kit^{(R)}$(Boeringer Manheim, Germany) and evaluated correlation between telomerase activity and tumor size, neck node metastasis, Anneroth malignancy score and influence of pre-operative chemotherapy on its activity in 27 cases of oral squamous cell carcinomas and 18 cases of normal oral epithelium. Also, correlation between telomerase activities and PCNA indices was evaluated. The results were obtained as follows: 1. The telomerase activities were detected in 24 specimens out of 27 oral squamous cell carcinoma specimens (88.9%) and in 5 specimens out of 18 normal oral epithelium specimens (27.8%). The mean value of telomerase activities was $0.9793{\pm}0.3428$ in 24 oral squamous cell carcinoma specimens and $0.4855{\pm}0.1117$ in 5 normal oral epithelium specimens. The positivity rate and mean value of telomerase activities in oral squamous cell carcinoma specimens were significantly higher than those of normal oral epithelium specimens (p<0.05). 2. There was no significant correlation between total Anneroth malignancy score and telomerase activity (p>0.05), but points of mitosis index and depth of invasion were significantly correlated with telomerase activities (p<0.05). 3. The positive immunohistochemical staining for PCNA(proliferating cell nuclear antigen) was observed in 26 specimens out of 27 oral squamous cell carcinoma specimens and mean value of PCNA indices of 26 specimens was $53.67{\pm}26.46$. PCNA indices were significantly correlated with telomerase activities (p<0.05). 4. The mean value of telomerase activities was significantly higher in pathologic T3/T4 group than in T1/T2 group (p<0.01). There was no significant difference of mean value of telomerase activities between pathologic neck node positive group and negative group (p> 0.05). Pre-operative chemotherapy significantly lowered the telomerase activities (p<0.05). The above results suggested telomerase activity could be used as diagnostic marker and adjunctive parameter for judging on histologic malignancy in oral squamous cell carcinoma.
Background: The decision of staging of esophageal cancer have great effect on the resectability of the lesion and estimation of the patient's prognosis. Today, CT is one of the most popular modality for staging of esophageal cancer. However, it has some limitations because of false-positive or false-negative findings on cancer staging. The purpose of this study was to analyze the efficacy of CT in preoperative staging of esophageal cancer. Material and Method: We retrospectively analysed the difference of staging of esophageal cancer between CT and histopathological findings for the 114 patients with histologically proven esophageal cancer who underwent operation at the department of thoracic and cardiovascular surgery, Chonnam national university hospital, between January 1999 and June 2003. We evaluated the efficacy of chest CT in the staging of esophageal cancer compared to postoperative histopathologic findings by calculating sensitivity, specificity, accuracy, and reproducibility of chest CT to detect abnormality. Result: The reproducibilities between chest CT and histopathologic findings were 0.32 (p<0.01) for primary tumor (T), 0.36 (p<0.01) for lymph node invasion (N), and 0.62 (p<0.01) for distant metastasis (M). The reproducibilities between chest CT and histopathologic findings for lymph node invasion (N) and distant metastasis (M) were superior to that of primary tumor (T). The accuracy of primary tumor (T) was 65.8% and 98.2% in group III and IV, which was significantly higher than that of group I and II (78.9% and 62.3%). In general, specificity of chest CT for TNM staging was superior to sensitivity. Conclusion: In conclusion, preoperative CT scanning can provide important information on lymph node invasion and metastasis of lesion than primary tumor invasion.
Purpose: This prospective study was performed to evaluate the usefulness of preoperative radioimmunoscintigraphy and intraoperative scintimetric examination (radioimmunoguided surgery: RIGS) using $^{99m}Tc-anti-CEA\;F(ab')_2$ fragment. Materials and Methods: Nineteen patients with rectal cancer underwent preoperative whole body planar scintigraphy at 4 hours after injection of $^{99m}Tc-anti-CEA\;F(ab')_2$ fragment and SPECT imaging at 18 hours. Surgical operation was performed at 24 hours after injection. During laparotomy, radioactivities from intraabdominal viscera were measured by gamma probe. The radioactivities from excised tumor and lymph nodes were also measured and compared with pathology. Results: All nineteen patients were confirmed to have adenocarcinomas in the rectum. Twenty-seven of 97 excised lymph node groups had metastasis and 2 patients had liver metastasis in pathology Preoperative radioimmunoscintigraphy detected primary tumors in 11 patients (sensitivity 55%) and it could not detect any lymph nodes or liver metastasis. All patients showed high radioactivity in the kidneys, liver, spleen, and major vessels in intraoperative measurement by gamma probe, and tumor activity was not discriminated from background activity However, radioactivity from excised tumor was higher than normal rectum (T/B ratio; $3.47{\pm}2.25$). When excised lymph node activity/background activity ratio >1.5 was considered as positive criteria of metastasis, sensitivity, specificity, positive and negative predictive values were 78.6%, 73.9%, 55.0% and 89.5%, respectively. Conclusion: Radioimmunoscintigraphy using $^{99m}Tc-anti-CEA\;F(ab')_2$ has no additional value for preoperative staging and use of early RIGS using $^{99m}Tc-anti-CEA\;F(ab')_2$ is inappropriate. For early RIGS using $^{99m}Tc$ labeled antibodies in rectal cancer patients, further development of more specific antibodies and methods to reduce background activity are needed.
Kim, Jin-Eui;Kim, Jung-Soo;Choi, Nam-Gil;Han, Jae-Bok
The Journal of the Korea Contents Association
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v.17
no.11
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pp.50-59
/
2017
To evaluate the capability of integrated PET-MRI, which has recently been utilized in the clinical practices, on the diagnosis of liver cancer, its utility was assessed by $2{\times}2$ decision matrix. The numbers of abnormal and normal decisions on the liver cancer were 98 and 51 cases, respectively, upon PET-MRI scan results of the subjects, and the numbers of positive and negative decisions were 103 and 62, respectively, upon cytopathologic results. Out of the two tests, 95 cases were shown as true-positive and 3 were false positive, while 62 were true negative and 5 were false negative. Upon the results of PET-MRI test, its sensitivity, specificity, false negative rate, and false positive rate were 95.00%, 95.38%, 0.05%, and 95.15%, respectively. Therefore, it is considered to have the high potential to use the determination of the stage before the surgery, detections of recurrence and remote metastasis, assessment of uncertain remote lymph node metastasis, and so on in the diagnosis of the liver cancer, and also for the clinical utility of PET-MRI to be sufficient by integrated diagnosis and follow up scan with pathological studies.
The aim of the study was to clarify the role of gastrokine 1 in the process of formation and development of gastric cancer. The expression of gastrokine 1 in gastric cancer and corresponding non-cancerous gastric tissues of 52 gastric cancer patients was assessed with the real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and immunohistochemistry. We also analyzed the relationship between the expression level and clinicopathological characteristics. Gastrokine 1 gene and protein expression in gastric cancer tissues was in both cases significantly lower than in corresponding non-cancerous gastric tissues (both P<0.01), but no significant relationship was found with clinicopathological parameters including tumor location, depth of invasion, differentiation, lymph node metastasis, stage, gender, age and carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) level in peripheral blood preoperation of patients (P>0.05, respectively). Furthermore, gastrokine 1 gene expression was markedly lower in gastric cancer tissues of Helicobacter pylori (HP)-positive patients than negative ones (P<0.05). The result of the study showed that gastrokine 1 might play a significant role in the process of formation and development of gastric cancer as an anti-oncogene. Its effect might be weakened by HP infection.
Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma, small cell lung carcinoma and neuroblastoma. Immunity against GD2 has anti-tumor activities, but GD2 is poorly immunogenic. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In our previous study, we produced anti-idiotypic antibodies mimicking GD2 (3A4 and 3H9), which induced humoral immunity. However, cellular immunity is essential to eradicate tumor cells in vivo as well as humoral immunity. In the present study, we investigated whether these anti-idiotypic antibodies 3A4 and 3H9 could induce cellular immunes responses. Methods: BALB/C mice were immunized with anti-idiotypic antibody 3A4 or 3H9, or normal mouse IgG as a negative control. Lymphoproliferative responses, cytokine production responses, and delayed-type hypersensitivity reactions were measured in mice immunized with the anti-idiotypic antibodies. Results: Both the anti-idiotypic antibody 3A4 and 3H9 induced GD2-specific lymphoproliferative responses and $IFN-{\gamma}$ production of lymph node lymphocytes in BALB/C mice. Only anti-idiotypic antibody 3H9 induced significant GD2-specific delayed-type hypersensitivity in the mice. Conclusion: These results show that anti-idiotypic antibodies 3A4 and 3H9 have the potentiality of inducing GD2-specific cellular immune responses that cannot be induced by the native antigen GD2 itself.
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.
Gaucher's disease is an autosomal recessive disorder resulting from mutation at the glucocerebrosidase locus on chromosome 1q21. As a result, glucocerebroside accumulates principally in the phagocytic cells known as Gaucher cells. In our case, a five-year old girl was admitted with seven days' history of fever and abdominal distension. At physical examination the patient had hepatosplenomegaly. Laboratory tests revealed a hemoglobin concentration of 2.8g/L: platelet counts of $23,000/{\mu}l$: normal range of white cell and differential counts, and negative Coombs' test. Liver enzymes were normal. For the evaluation of hepatosplenomegaly, fine needle aspiration was performed blindly against the palpable spleen. Wet-fixed hematoxylin and eosin-stained smears are made. The smears from the spleen showed predominantly macrophages with abundant cytoplasm and rather small, uniform, often eccentric nuclei with small nucleoli. The multinucleated cells were often found. The cytoplasm was pale, with more or less distinct fibrillarity. The cells had the characteristic appearance of Gaucher cells. Gaucher cells were also found in the tissue section from the liver, spleen and lymph node and the bone marrow aspirate. The diagnosis was later confirmed by determination of bela-glucosidase activity in peripheral blood leucocytes. Fine needle aspiration of the spleen is considered as a convenient procedure with a low complication rate for the diagnosis of lysosomal storage disease.
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