Drug resistance is the main restriction factor for clinical usage of taxanes.This review concentrates on drug-resistance mechanisms of taxanes that include drug target change,avidity change between drug-target interaction,decrease of cellular effective drug concentration,downstream cellular responses to a drug target molecular lesion,and cell cycle regulation-mediated drug resistance.

Objective To retrospectivel y analyze the abdominal CT findings and pathological results of the chronic schist osomiasis so as to improve the diagnostic accuracy of the disease. M ethods The plain abdominal CT scanning was performed in 103 cases an d enhanced CT scanning in 81 cases. The pathological specimen which was consist ent with the section of CT scan was obtained in each cases. Results On CT scanning, liver cirrhosis was seen in 84 cases, various calci fication in liver in 71 cases, liver cancer in 12 cases, enlargement of sple en in 78 cases, calcification in spleen in 13 cases, wall-thickening in colon i n 27 cases, calcification in colon in 31 cases, and colon cancer in 9 cases. Pa thological examination revealed various fibrosis and formation of pseudolobule. The eggs and calcification could be seen in pseudolobule and septa, colonic sub mucosa, and regional lymph nodes. Fibrous hyperplasia in colonic wall and hyper plasia in mucous membrane were obvious. Fibrous hyperplasia and calcification w ere seen in spleen, but the eggs were not found. Conclusion The liver and colon are the major organs affected by chronic schistosomias is in abdomen, and the CT findings are obvious too. The pathological features o f spleen are accompanied with liver cirrhosis. CT is the important imaging meth od in diagnosing chronic schistosomiasis and pathological changes.

AIMStudy on the relationship between the degraded spinal cord injuries and the changes of the motor evoked potentials (MEP) to prove the diagnosis and prognosis value of MEP.

METHODSAfter injury at T8-T9 cord using modified Allen's weight-drop method, 27 male SD rats were divided randomly into control group (n = 5), group A (50 gcf, n = 8), group B (70 gcf, n = 8) and group C (100 gcf, n = 6). MEPs elicited by monopolar transcortical stimulation were recorded continuously before injury, just after injury, 15 minutes, 1 hour, 3 hours and 6 hours after injury. The rate of the size of the bleeding or necrosis area to the total cord was also calculated.

RESULTSMEP had no significant change in the control group. The amplitude of MEP's early components in group A or group B decreased or even obliterated after SCI, and then partially recovered, while the late components were lost without any recovery signals. All animals in group C showed no MEP waves excepting 2 rats had recovery signals. The size of the cord injuries area increased according to the dropping force and was correlated significantly with the amplitude of the largest peaks of scMEP 1 hour after SCI (r = -0.821).

CONCLUSIONThe scMEP changes after SCI are correlated with the injury forces and the pathological changes in the cord, which indicates that scMEP can be used as an objective index for the cord functional monitoring.

Animals ; Electric Stimulation ; Evoked Potentials, Motor ; physiology ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; pathology ; physiopathology

Aged ; Female ; Femoral Neck Fractures ; diagnostic imaging ; surgery ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Radiography ; Retrospective Studies ; Treatment Outcome

The transforming growth factor β1 (TGF-β1) and CD8-positive T cells are two important immune factors that function at opposite directions. The purpose of this study was to verify the relationship between the two factors and their associations with long-term effects of adjuvant chemotherapy or endocrine therapy in breast cancer. Expression of TGF-β1 precursor and CD8 was immunohistochemically detected on surgically-obtained tumor samples of 130 (stage I-III) invasive breast carcinomas from Chinese subjects, who were followed up for a mean time of 112 months. Interstitial CD8-positive cells and TGF-β1 precursor-positive cells adjacent to tumor nests were counted. Infiltration of CD8-positive lymphocytes into tumor nests and TGF-β1 precursor expression in tumor cells were observed and survival analysis was performed. Our results showed that density of interstitial CD8-positive lymphocytes was an independent adverse prognostic factor for distant disease-free survival (DDFS) (HR=8.416, 95% CI=1.636-43.292, P=0.011) in hormone receptor-positive patients who were on adjuvant endocrine therapy. For breast cancer patients who did not receive adjuvant chemotherapy, those without infiltration of CD8-positive cells into tumor nests had a shorter overall survival (OS) than their counterparts with CD8-positive cell infiltration into tumor nests (Log-Rank, P=0.003). But OS of patients without infiltration of CD8-positive cells into tumor nests was significantly prolonged by adjuvant chemotherapy (Log-Rank, P=0.013) and paralleled that of patients with CD8-positive cell infiltration. Although OS was shorter in the tumor cell TGF-β1 precursor (t-TGF-β1-pre)-positive patients than in the negative patients in patients without receiving chemotherapy (P=0.053), OS of t-TGF-β1-pre-positive patients was significantly prolonged by adjuvant chemotherapy (P=0.035) and was longer than that of t-TGF-β1-pre-negative patients. Analysis showed that t-TGF-β1-pre was an independent positive prognostic factor for DDFS (HR=0.392 95% CI=0.157-0.978, P=0.045) in patients who received adjuvant chemotherapy. This study suggested that density of interstitial CD8-positive lymphocytes was of prognostic value in hormone receptor-positive patients who received adjuvant endocrine therapy. Our study verified that adverse immunologic signatures consisting of absence of CD8-positive cells in tumor nests or expression of TGF-β1 precursor in tumor cells in breast cancer were associated with worse prognosis and significantly improved long-term survival with adjuvant chemotherapy, respectively.
Biomarkers, Tumor ; metabolism ; Breast Neoplasms ; drug therapy ; metabolism ; surgery ; CD8-Positive T-Lymphocytes ; metabolism ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Middle Aged ; Outcome Assessment (Health Care) ; methods ; statistics & numerical data ; Prognosis ; Proportional Hazards Models ; Protein Precursors ; metabolism ; Retrospective Studies ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo assess and compare the prognostic role of tumor-infiltrating T lymphocytes in stage 1-3 breast cancer.

METHODSParaffin sections were retrospectively collected from 130 cases of stage 1-3 breast cancer patients who received surgery between January 2000 and December 2002 in General Hospital of the People's Liberation Army. Immunohistochemistry was used to assess the density of tumor-infiltrating lymphocytes(TILs) that were positive of CD4 and CD8. These variables were evaluated for their association with histopathologic features along with overall survival(OS) , distant disease-free survival(DDFS) and disease-free survival(DFS) .

RESULTSIntraepithelial CD4+lymphocytes infiltration was an independent prognostic factor for DFS(HR=0.248, 95%CI=0.113-0.543, P=0.000) , DDFS(HR=0.361, 95%CI=0.157-0.830, P=0.017) , and OS(HR=0.297, 95%CI=0.119-0.741, P=0.009) in multifactor COX regression model. In hormone receptor negative group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=0.286, 95%CI=0.101-0.807, P=0.018) and DDFS(HR=0.293, 95%CI=0.104-0.825, P=0.020) , respectively. In hormone receptor positive group, mesenchymal CD8+lymphocytes and intraepithelial CD8+lymphocytes were independent prognostic factors for OS(HR=4.854, 95%CI=1.435-16.415, P=0.011) and DDFS(HR=10.493, 95%CI=1.226-89.795, P=0.032) respectively. Further analysis found that OS of hormone receptor positive patients with lower mesenchymal CD8+TILs was significantly proved by adjuvant endocrine therapy.

CONCLUSIONSIn the current investigation, intraepithelial CD4+TILs demonstrated independent prognostic significance for survival. CD8+TILs were associated with better survival in hormone receptor negative patients but associated with worse survival in hormone receptor positive patients. The long-term clinical effects of adjuvant endocrine therapy is related with density of mesenchymal CD8+TILs and in turn affected prognostic value of mesenchymal CD8+TILs.

Adult ; Aged ; Aged, 80 and over ; Breast Neoplasms ; diagnosis ; pathology ; therapy ; CD4-Positive T-Lymphocytes ; pathology ; CD8-Positive T-Lymphocytes ; pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Lymphocytes, Tumor-Infiltrating ; pathology ; Middle Aged ; Prognosis ; Retrospective Studies

Purpose To investgate the expression and clinical significance of GFRα3 in esophagus squamous cell carcinoma (ESCC).Methods Expression of GFRα3 in 114 esophagus squamous cell carcinoma,17 cases of high grade intraepithelial neoplasia and Tis,25 cases nomal tissue was detected by immunohistochemistry.Expression of GFRα3 in 12 paired flesh tissues had also been determined by Western-blot.Results The positive expression of GFRα3 in nomal esophageal tissues,high grade intraepithelial tissues and Tis was 0,29.4％,76.3％ respectively by immunohistochemistry.Expression of GFRα3 in carcinomatous tissues was higher than that of adjacent tissues (P ＜ 0.05).Moreover,the expression of GFRα3 was significantly associated with depth of invasion,higher clinical stage and survival outcome of patients with ESCC.Conclusion The expression of GFRα3 maybe a useful predictor of disease depth of invasion,progression and outcome in ESCC.

OBJECTIVETo investigate the way of resection of high-sacrum tumors and the way and duration of the spinal-pelvic TSRH or ISOLA internal fixation.

METHODFrom October 1998 through April 2002, 35 patients with sacral tumor were enrolled in our hospital, including 4 cases in L(5)-S(1), 2 in L(5)-S(2), 4 in S(1), 8 in S(1 - 2), 6 in S(1 - 3), 6 in S(1 - 4), 5 in S(1 - 5). 35 patients were followed by lumbo-pelvic TSRH or ISOLA internal fixation and corresponding chemotherapy and radiotherapy.

RESULTSIn the follow-up period of 6 - 42 months, the short-term results were satisfactory with the lumbosacral pain reduced and the neurological function improved in different degrees, however dysuria occurred in 1 case and skin necrobiosis at coccygeal incision occurred in 1 case; two cases experienced cerebrospinal fluid leakage and 1 case experienced postoperative infection and delayed healing, 1 case with chordoma and 2 cases with malignant fibrous histiocytoma recurred 1 year after postoperation, one of these 2 cases with malignant fibrous histiocytoma suffered from lung metastasis and died of system failure 19 months after postoperation. No fractured rod occurred.

CONCLUSIONSurgical procedure and postoperative comprehensive treatment have important effects on the prognosis. High-sacral tumor resection and reconstruction are effective means of achieving stabilization, providing significant pain relief and preserving ambulatory capacity.

Adolescent ; Adult ; Aged ; Female ; Follow-Up Studies ; Fracture Fixation, Internal ; methods ; Humans ; Lumbar Vertebrae ; Male ; Middle Aged ; Pelvic Bones ; surgery ; Sacrum ; Spinal Neoplasms ; surgery ; Treatment Outcome ; Young Adult

The purpose of this study was to investigate the effects of vasonatrin peptide (VNP) on electrically-induced intracellular calcium ([Ca(2+)](i)) transient and mechanism of the effects in the cardiac myocytes. The [Ca(2+)](i) transient was measured with a fluoremetric method. The effects of HS-142-1, 8-Br-cGMP and methylene blue (MB) on [Ca(2+)](i) transient in cardiac myocytes were also determined. Isoproterenol (Iso) at 10(-10)~10(-6) mol/L augmented electrically-induced [Ca(2+)](i) transient dose-dependently, which was (13+/-8)% (P>0.05), (26+/-13)% (P< 0.05), (66+/-10)% (P<0.01), (150+/-10)% (P<0.01) and (300+/-25)% (P<0.01), respectively. These effects were blocked by an beta-adrenergic bloker propranolol (10(-6) mol/L). The effect of Iso (10(-8) mol/L) on [Ca(2+)](i) transient was attenuated in a dose-dependent manner by VNP at 10(-10)~10(-6) mol/L, which was (99+/-3)% (P>0.05), (96+/-2)% (P<0.05), (84+/-6)% (P<0.01), (66+/-3)% (P<0.01) and (62+/-3)% (P<0.01), respectively. 8-Br-cGMP (10(-7)~10(-3) mol/L) aslo attenuated 10(-8) mol/L Iso-induced [Ca(2+)](i) transient dose-dependent. The effect of VNP on [Ca(2+)](i) transient was almost abolished in the presence of HS-142-1 (2x10(-5) mol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptors. MB (10(-5) mol/L), an inhibitor of GC, not only blocked the effect of VNP in myocytes, but also augmented electrically-induced [Ca(2+)](i) transient. VNP and HS-142-1 themselves did not change the [Ca(2+)](i) transient in the cardiac myocytes significantly. But MB augmented the [Ca(2+)](i) transient in the cardiac myocytes significantly. These results suggest that VNP attenuates [Ca(2+)](i) transient induced by Iso. This effect is possibly achieved by binding VNP with the natriuretic peptide GC receptors in the myocytes, leading to an increase in intracellular cGMP.
Animals ; Atrial Natriuretic Factor ; pharmacology ; Calcium ; metabolism ; Calcium Channels ; metabolism ; Cyclic GMP ; metabolism ; Depression, Chemical ; Female ; Guanylate Cyclase ; metabolism ; Isoproterenol ; pharmacology ; Male ; Myocytes, Cardiac ; metabolism ; Rats ; Receptors, Atrial Natriuretic Factor ; metabolism

OBJECTIVETo study the surgical indications, approaches and the clinical results of the total spondylectomy and instrumentation reconstruction in the treatment of cervical spinal tumor.

METHODSFrom October 1998 to October 2003, 39 patients with lower cervical bone tumors, including 34 cases with primary tumor and 5 cases with metastatic tumor, were admitted and operated on with total spondylectomy. The patients underwent anteroposterior total spondylectomy including anterior cervical plating, titanium mesh reconstruction and posterior instrumentation based on the location of tumor lesions in the lower cervical spine. One vertebral level total spondylectomy was performed in 29 cases, two level in 7 cases and three level in 3 cases.

RESULTSThe postoperative follow-up ranged from 6 months to 4 years. A majority of patients achieved good results postoperatively. Nineteen cases had complete relief of neurological status. One patient died of multiple metastases and systemic failure 24 months later. One case with malignant neurilemmoma developed local recurrence one year postoperatively.

CONCLUSIONAnteroposterior total spondylectomy and reconstruction can reduce local recurrence, improve neurological function and increase operation therapeutic effect. Meanwhile, the technique of cervical total spondylectomy carries relatively greater risks and should be more attention to the operation indication.

Adolescent ; Adult ; Aged ; Cervical Vertebrae ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Spinal Fusion ; methods ; Spinal Neoplasms ; pathology ; surgery ; Treatment Outcome