Heat fixation of cancer cells ablated with high-intensity-focused ultrasound in patients with breast cancer

BACKGROUND: High-intensity-focused ultrasound (HIFU) is a noninvasive thermal ablation technique. This study reports the use of histological techniques for the pathological assessment of HIFU effects in patients with breast cancer. METHODS: Twenty-three patients with biopsy-proven breast cancer underwent HIFU treatment for primary breast lesion. Mastectomy was performed on all patients after HIFU. By using histological examinations, the surgical specimens were assessed to explore HIFU effects on breast cancer. RESULTS: Coagulation necrosis of targeted tumors was confirmed by microscopy in 23 patients. Tumor cells presented typical characteristics of coagulation necrosis in the peripheral region of the ablated tumor in all patients. However, in 11 of 23 patients, hematoxylin and eosin staining showed normal cellular structure in the central ablated tumor. By using electronic microscopy and nicotinamide adenine dinucleotide-diaphorase stain, those who had normal-appearing cancer cells were not viable. CONCLUSIONS: HIFU can cause the heat fixation of ablated tumor through thermal effect.     

The effects of estrogen on human breast carcinomas serially transplanted into nude mice

The effect and mechanisms of 17β-estradiol (E₂) on breast cancer cells were studiedin vivo andin vitro, using 5 human breast carcinomas serially transplanted into nude mice. These carcinoma strains consisted of 4 estrogen receptor (ER) positive tumors and 1 ER negative tumor. Mice bearing these tumors were treated with an intramuscular injection of E₂ at a dosage of 50 mg/kg and the tumor doubling time (Td) was calculated in days. The tumor growth was significantly stimulated by E₂ in 3 out of the 4 ER positive tumors, the Td of the E₂ treated groups being 17.6 days for MCF-7 (control: −17.8 days), 12.8 days for R-27 (control: −12.5 days∼14.5 days) and 10.4 days for Br-10 (control: 14.5 days), however, in the T-61 tumor, the growth was inhibited by E₂ in a dose dependent manner. In the case of the ER-negative MX-1 tumor, the tumor cell growth was not affected by E₂. Discrepancies between the effects of E₂ on ER-positive tumors were further analyzed by examining the steroid hormone receptor status and conductingin vitro growth studies.In vitro clonogenic cell assay reproduced the antitumor activity of E₂, indicating that E₂ directly inhibits part of the cell growth of T-61 tumors. The above results suggest that this experimental system provides a useful tool for analyzing the mechanism of estrogen in breast cancer and that the clonogenic assay using ER positive specimens can help to identify breast cancers sensitive to estrogen therapy.     

A Phase II Trial of Image-Guided Radiofrequency Ablation of Small Invasive Breast Carcinomas: Use of Saline-Cooled Tip Electrode

Background Local ablative therapy of breast cancer represents the next frontier in the evolution of minimally-invasive breast conservation therapy. We performed this Phase II trial to determine the efficacy and safety of Radiofrequency (RF) ablation of small invasive breast carcinomas. Methods Seventeen patients with biopsy-proven invasive breast cancer, ≤ 1.5 cm in diameter were enrolled in this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding breast tissue were ablated with saline-cooled RF electrode followed by surgical resection. Pathologic and immunohistochemical stains were performed to assess tumor viability. We examined whether loss of ER, PR receptor and pancytokeratin expression following RF ablation would correlate with non-viability. Results Fifteen patients completed the treatment. The mean tumor size was 1.28 cm. The mean ablation time was 21 minutes using a mean power of 35.5 watts. During ablation, the tumors became progressively echogenic that corresponded with the region of severe electrocautery injury at pathological examination. Of the 15 treated patients, NADPH viability staining was available for 14 patients and in 13 (92.8%), there was no evidence of viable malignant cells. ER, PR expression and pancytokeratin immunohistochemistry analysis were unreliable surrogates for determining non-viability. Following RF ablation, 2 patients developed skin puckering. Conclusions RF ablation is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. Further research is necessary to optimize this image-guided technique and evaluate its future role as the sole local therapy.     

高强度聚焦超声治疗兔乳腺移植瘤后残留肿瘤对机体的影响

目的观察高强度聚焦超声（HIFU）治疗兔乳腺移植瘤后残留肿瘤对机体的作用。方法将33只实验兔分为HIFU组、手术组和对照组,分别用HIFU消融和手术切除的方法建立兔乳腺移植瘤治疗后肿瘤残留模型,病理检查确认消融效果。治疗后观察存活时间及肿瘤转移情况。结果HIFU组平均存活时间、8周存活率、腋淋巴结转移时间均长于手术组和对照组（P〈0.05）,手术组、对照组比较差异无统计学意义（P〉0.05）。结论HIFU治疗肿瘤后能有效抑制残留肿瘤的生长和转移,延长荷瘤兔生存时间。     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Preliminary Experience Using High Intensity Focused Ultrasound for the Treatment of Patients With Advanced Stage Renal Malignancy

PurposeWe present the preliminary results of patients with advanced stage renal malignancy treated with high intensity focused ultrasound (HIFU), and investigate the safety and feasibility of using HIFU in the treatment of selected patients with renal tumors.Materials and MethodsHIFU treatment was performed in 12 patients with advanced stage renal cell carcinoma and 1 patient with colon cancer metastasized to kidney. Patients were followed after treatment to observe complications and long-term therapeutic efficacy. Complications and changes in symptoms seen at presentation were recorded. Mid stream urine specimens were sent for microscopy and serum creatinine was measured postoperatively. Followup radiological examinations were performed to detect tumor response to the ablation.ResultsA total of 13 patients received HIFU treatment safely, including 10 who had partial ablation and 3 who had complete tumor ablation. After HIFU hematuria disappeared in 7 of 8 patients and flank pain of presumed malignant origin disappeared in 9 of 10 patients. Postoperative images showed decrease in or absence of tumor blood supply in the treated region and significant shrinkage of the ablated tumor. Of the 13 patients 7 died (median survival 14.1 months, range 2 to 27) and 6 were still alive with median followup of 18.5 months (range 10 to 27).ConclusionsThis preliminary experience suggests that HIFU could be safe and feasible in the treatment of patients with advanced renal malignancy.     

Results and side effects of high-intensity focused ultrasound in localized prostate cancer

At the time of diagnosis, prostate cancer is organ confined in 70% of the cases. A quarter of these patients undergo local therapy (surgery/radiation); 75% risk disease progression by "watchful waiting" or systemic side effects through hormonal ablation. Local high-intensity focused ultrasound (HIFU), as minimal invasive tissue coagulation (85 degrees C), ablates prostatic tissue with high precision. Since April 1996, 184 patients have undergone 232 sessions of transrectal HIFU therapy (average 90 min) under spinal anesthesia at 2.25/3.0 MHz, 50 W, and a penetration depth of 25 mm. The follow-up serum prostate specific antigen (PSA) concentration, sextant biopsies, International Prostate Symptom Score (IPSS), quality of life measures (QoL), and complaint registration provide the foundation for this clinical evaluation. Follow-up sextant biopsies (an average of 1.9) showed 80% of the patients to be cancer free. In men with residual cancer, the tumor mass was reduced more than 90%. The PSA nadir in 97% was <4 ng/mL, including 61% with values <0.5 ng/mL. After primary HIFU, no severe side effects (fistula, second or third grade incontinence, rectal mucosal burns) occurred. All patients had a suprapubic tube (average 29 days), and 33% needed a transurethral debris resection averaging 7 g. They were discharged within 23 hours. According to the short-term follow-up transrectal HIFU enables minimal invasive local prostate tissue ablation with high rates of negative biopsies, low PSA nadir, and low complication rate.     

高强度聚焦超声联合纳米微泡造影剂对兔VX2乳腺移植瘤辐照效果的影响

目的观察高强度聚焦超声（HIFU）联合纳米微泡对兔VX2乳腺移植瘤辐照效果的影响。方法制备纳米微泡,于光镜、电镜下观测微泡的大小、形态、分布及稳定性。采用Zeta SIZIER 3000电位仪测定微泡的粒径、电位。60只健康纯种雌性新西兰白兔,麻醉后种植VX2肿瘤于双侧乳腺组织内。2周后,选取乳腺区肿瘤组织直径大小为10mm的兔进行实验,随机分为实验组（HIFU＋纳米微泡）和对照组（HIFU＋磷酸盐缓冲液）,辐照剂量150 W,辐照时间5s,记录HIFU辐照前后灰阶变化,辐照后行HE染色观察坏死区域大小,并进行统计学分析。结果成功制备纳米微泡,其理化性质稳定,粒径大小合理,电位均衡。实验组靶区平均灰度差明显高于对照组（P〈0.05）。HE染色示实验组发生凝固性坏死范围明显大于对照组（P〈0.001）。结论纳米微泡能明显增强的损伤效果。     

Clinical study on the effect of intratumoral administration of OK-432 on breast cancer--anti-tumor immune response at the site of local injection]

To elucidate the mechanism of tumor reduction and local immune response after administration of OK-432 into the lesions of breast cancer, patients were given intratumoral injection of OK-432 before surgery. And precise identification of infiltrative lymphocytes was performed. The subjects were 25 patients with primary breast cancer. These patients were randomly divided into the following 3 groups: 10 patients given intratumoral injection of OK-432, 5 patients given intratumoral injection of physiological saline and 10 patients give no treatment. After operation frozen specimens of each tumor were subjected to simple immunohistochemical staining with Leu 2a, Leu 3a and Leu 7, and to immunohistochemical double staining with combination of Leu 2a x Leu 15 and Leu 3a x Leu-DR. Examination of infiltrative lymphocytes in the tumor revealed the positive rate was 100% for Leu 2a + cells (strongly positive, 70%), 90% for Leu 3a + cells (strongly positive, 70%) and 90% for Leu 7 + cells (strongly positive, 0%) in patients given intratumoral injection of OK-432. Double staining showed cytotoxic T cells and helper T cells were predominant among Leu 2a + cells and Leu3a + cells, respectively. Cytotoxic T cells, helper T cells and NK cells were induced at the tumor site after intratumoral injection of OK-432, suggesting the antitumor immune response of these cells is involved in tumor reduction following local administration of OK-432.     

Expression of MAGE antigens and analysis of the inflammatory T-cell infiltrate in human seminoma

The MAGE gene family encodes antigens that are recognized by cytotoxic T-cells. The expression of MAGE antigens has been linked to tumor stage, and MAGE peptides are under investigation as possible vaccines. Seminomas are tumors that are typically accompanied by a heavy inflammatory infiltrate, but have not been studied with regard to their MAGE antigen expression and its correlation with the inflammatory infiltrate. We investigated, therefore, MAGE protein expression, the amount of cytotoxic T-cells, clonality of the lymphocytic infiltrate, apoptotic activity and occurrence of necrosis. Specimens of 27 patients with classical seminoma were examined by immunohistochemistry for CD4, CD8, CD56, CD45R0, β₂-microglobulin and HLA-DR. MAGE expression was detected with the monoclonal antibody 57B, reactive with MAGE-1, -3, -4, -6 and -12. Clonality of the inflammatory infiltrate was examined by multiplex polymerase chain reaction (PCR) analysis of the T-cell receptor rearrangement. Apoptotic cells were detected by DNA nick-end labeling of fragmented DNA, and the apoptotic index was determined semi-quantitatively. Expression of 57B was found in 19 (70%) of 27 seminomas. In all cases, more than 70% of T-cells expressed CD45R0. In four cases, a predominant infiltration of CD8-positive cytotoxic T-cells (CD4/CD8 ratio <1) was present. However, 15 seminomas showed a CD4/CD8 ratio >1. In all cases, infiltration of CD56-positive natural killer cells was only focal. HLA-DR expression was not detectable in tumor tissue; β₂-microglobulin was only focal in three cases. Analysis of the T-cell clonality revealed a polyclonal population. The apoptotic index was not significantly different in 57B-positive seminomas (4.15%) compared with 57B negative seminomas (3.80%). Also, no correlation between the 57B expression and the occurrence of necrosis was found. MAGE antigens are homogeneously expressed in most seminomas, but their presence does not appear to represent a dominant epitope responsible for the lymphocytic infiltrate. Received: 11 April 2000 / Accepted: 1 August 2000     

The utility of intraoperative contrast-enhanced ultrasound in detecting residual disease after focal HIFU for localized prostate cancer

Background and objectivesFocal high intensity focused ultrasound (HIFU) is an emerging treatment for selected men with localized prostate cancer. A limitation of HIFU is the absence of a reliable tool to measure treatment effect intraoperatively. Contrast-enhanced ultrasound (CEUS) has been shown to be a promising modality for assessing the extent and boundaries of tissue ablation. The aim of this study was to assess the value of CEUS immediately after focal HIFU.Materials and methodsRetrospective analysis of a prospectively maintained registry including consecutive men undergoing focal HIFU (Focal One). Candidates for focal HIFU were treatment naive men with ≥10 years life expectancy, prostate-specific antigen (PSA) ≤ 20 ng/ml, TNM primary tumor, regional lymph nodes, distant metastasis stage ≤ T2c N0 M0 with a multiparametric MRI (mpMRI) visible lesion concordant with histologically proven prostate cancer. CEUS evaluation was performed immediately at the end of the procedure. Based on the surgeon's estimation of CEUS imaging, re-HIFU was performed, followed by another CEUS evaluation. To test our hypothesis, the results of the CEUS were compared to the results of early mpMRI to rule out clinically significant cancer. The concordance between the 2 tests was measured using the Cohen's kappa. The best model including relevant predictors was calculated with CEUS or with mpMRI to determine their respective added value.ResultsOf 66 men who underwent HIFU, 32 met eligibility criteria. Bifocal treatment was performed in 1 man, increasing the number of treated lesions to 33. Further ablation based on CEUS was delivered intraoperatively to 13 lesions (39%). The positive biopsy rate for clinically significant cancer in the treated zones was 30% (10/33). The negative predictive value of CEUS and early mpMRI was 71% (95% confidence interval: 59%–82%). Concordance between CEUS and mpMRI was significant with a 72.7% agreement (P = 0.001). The model with CEUS showed the best accuracy with an area under the curve of 0.881.ConclusionCEUS has a higher added value compared to early mpMRI in ruling out clinically significant cancer after focal HIFU. It should be evaluated whether the use of CEUS intraoperatively enhances the efficacy of focal HIFU.     

Radiofrequency Thermal Ablation of Breast Cancer Local Recurrence: A Phase II Clinical Trial

Background  The role of radiofrequency (RF) ablation to treat local recurrence of breast cancer is unknown. Methods  We conducted a two-stage phase II clinical trial. Eligible patients had a histologically confirmed noninflammatory and ≤3 cm ipsilateral breast tumor recurrence. The tumor site was identified by intraoperative sonography. A LeVeen needle electrode (RadioTherapeutics Corp, Mountain View, Calif) was inserted into a single site within the tumor and radiofrequency ablation was performed using a RF-2000 generator (RadioTherapeutics Corp). After completion of radiofrequency, a mastectomy was performed. Conventional staining and nicotinamide adenine dinucleotide-diaphorase (NADH-diaphorase) cell viability staining were performed. Results  During the first stage, procedures were uneventful. Conventional, cytokeratin, and NADH-diaphorase staining identified persistent viable tumor cells in the RF-ablated region in three patients. This phase II trial was stopped after completion of the first stage because of insufficient efficacy. Conclusion  We demonstrate in this study that RF ablation is a potential technique to destroy local recurrence of breast tumors but the technique we tested in this phase II clinical trial had insufficient efficacy to recommend its use in routine.     

经直肠高强度聚焦超声系统治疗前列腺癌57例疗效分析

目的:探讨经直肠高强度聚焦超声系统(HIFU)治疗PCa的疗效。方法:使用Sonablate500型经直肠HIFU治疗系统,对57例PCa患者进行HIFU治疗,其中局限性PCa27例,晚期PCa30例。在确定生化复发之前,对局限性PCa仅行经直肠HIFU治疗;对于晚期PCa,在行经直肠HIFU治疗的同时,联合应用内分泌治疗。结果:HIFU治疗平均手术操作时间为111(86～153)min,平均术后住院时间为3.2(2～18)d。平均随访时间18(6～30)个月。局限性PCaHIFU治疗后,生化检查阴性率(PSA(4.0μg/L)在治疗后的1、2、3年分别为86%、81%和79%。30例晚期PCa治疗平均8个月(3～24个月)后,26例血清PSA<4.0μg/L(其中20例血清PSA<0.5μg/L)、21例患者前列腺体积缩小>50%。治疗后6个月时与治疗前相比,前列腺体积缩小、PSA水平降低、Qmax增加及IPSS改善差异均有显著性(P<0.05)。HIFU治疗后无严重尿道直肠瘘、尿失禁等并发症发生。结论:经直肠HIFU治疗PCa,安全、有效,并发症少,近期疗效较好,是一种可选择的PCa微创治疗方法。     

Tumor Regression and Autoimmunity in Patients Treated With Cytotoxic T Lymphocyte–Associated Antigen 4 Blockade and Interleukin 2: A Phase I/II Study

Background Cytotoxic T lymphocyte–associated antigen (CTLA)-4 can inhibit T-cell responses and is involved in tolerance against self antigens. We previously reported autoimmune manifestations and objective cancer regressions in patients with metastatic melanoma treated with CTLA-4 blockade. The possibility of activating tumor-reactive T cells while removing inhibitory activity with CTLA-4 blockade has stimulated interest in using anti–CTLA-4 antibodies in combination with other cancer immunotherapies to improve clinical outcomes. In this study, we assessed the antitumor activity and autoimmune toxicity of CTLA-4 blockade in combination with an immune-activating stimulus, interleukin (IL)-2, in patients with metastatic melanoma. Methods Thirty-six patients received anti–CTLA-4 antibody every 3 weeks. Three patients per cohort received doses of .1, .3, 1.0, and 2.0 mg/kg. Twenty-four patients received 3.0 mg/kg. All patients received IL-2 therapy (720,000 IU/kg every 8 hours to a maximum of 15 doses). Results Eight patients (22%) experienced objective tumor responses (three complete and five partial), including metastases in the lungs, lymph nodes, mediastinum, and subcutaneous tissues. Six of the eight patients have ongoing objective responses at 11 to 19 months. Five patients (14%) developed grade III/IV autoimmune toxicities secondary to anti–CTLA-4 administration, including four patients with enterocolitis and one with arthritis and uveitis. Conclusions There is not evidence to support a synergistic effect of CTLA-4 blockade plus IL-2 administration, because the 22% objective response rate is that expected from the sum of these two agents administered alone. Durable cancer regressions were seen in patients treated with this combination.     

高强度聚焦超声联合赛来昔布治疗胰腺癌裸鼠移植瘤的实验研究

目的研究高强度聚焦超声（HIFU）联合选择性环氧合酶-2抑制剂赛来昔布对胰腺癌裸鼠移植瘤生长的影响。方法40只裸鼠建立胰腺癌裸鼠移植瘤模型，随机分对照组、HIFU组、赛来昔布组及联合组共观察40d，研究各处理因素对移植瘤生长的影响。观察4组移植瘤组织病理学变化，RT-PCR检测bcl-2、bax及HSP70的表达，免疫组化检测HSP70的表达。结果联合组移植瘤平均体积最小，赛来昔布组、HIFU组、联合组抑瘤率分别为81．3％、93％、99．7％。病理示HIFU组和联合组中见大片凝固性坏死，HIFU组可见残留癌细胞小岛而联合组未见。FT-PCR示bcl-2在各组中均表达极弱；bax在HIFU组、赛来昔布组及联合组中表达均上调；HSP70以联合组表达上调最明显。免疫组化示HIFU组、联合组HSP70呈强阳性表达。结论HIFU与赛来昔布联合对胰腺癌裸鼠移植瘤的治疗可起到协同作用。HIFU不仅可以直接杀灭肿瘤细胞，而且可以通过上调bax的表达诱导肿瘤细胞凋亡；通过上调HSP70的表达激发机体的免疫反应进一步抑制肿瘤生长。     

Radiofrequency Ablation of Invasive Breast Carcinomas: A Phase II Trial

Background Local ablative therapy of breast cancer represents the next frontier in the minimally invasive breast-conservation treatment. We conducted a phase II trial to evaluate radiofrequency ablation (RFA) of invasive breast carcinomas. Methods Consecutive patients from two Mexican Institutions with invasive breast cancers < 4 cm, with no multicentric tumors and no previous chemotherapy were included in this trial. Under ultrasound guidance, the tumor and a 5 mm margin of surrounding breast tissue were ablated with saline-cooled RFA electrode followed by surgical resection. Routine pathologic analysis and viability evaluation with NADPH-diaphorase stain were performed to assess tumor ablation. Procedure-associated morbidity was recorded. Results Twenty-five patients were included. Mean patient age was 55.3 years (range 42–89 years). Mean tumor size was 2.08 cm (range 0.9–3.8 cm). Fourteen tumors (56%) were <2 cm. The mean ablation time was 11 minutes using a mean power of 35 W. During ablation, the tumors become progressively echogenic that corresponded with the region of severe RFA injury at pathologic examination. Of the 25 patients treated, NADPH stain showed no evidence of viable malignant cells in 19 patients (76%), with significant difference between tumors <2 cm (complete necrosis in 13 of 14 cases, 92.8%) vs. those >2 cm (complete necrosis 6 of 11 cases, 54.5%) (P < .05). No significant morbidity was recorded. Conclusions RFA is a promising minimally invasive treatment of small breast carcinomas, as it can achieve effective cell killing with a low complication rate. Further studies are necessary to optimize the technique and evaluate its future role as local therapy for breast cancer.     

Noncanonical TGF-β Signaling During Mammary Tumorigenesis

Breast cancer is a heterogeneous disease comprised of at least five major tumor subtypes that coalesce as the second leading cause of cancer death in women in the United States. Although metastasis clearly represents the most lethal characteristic of breast cancer, our understanding of the molecular mechanisms that govern this event remains inadequate. Clinically, ~30% of breast cancer patients diagnosed with early-stage disease undergo metastatic progression, an event that (a) severely limits treatment options, (b) typically results in chemoresistance and low response rates, and (c) greatly contributes to aggressive relapses and dismal survival rates. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that regulates all phases of postnatal mammary gland development, including branching morphogenesis, lactation, and involution. TGF-β also plays a prominent role in suppressing mammary tumorigenesis by preventing mammary epithelial cell (MEC) proliferation, or by inducing MEC apoptosis. Genetic and epigenetic events that transpire during mammary tumorigenesis conspire to circumvent the tumor suppressing activities of TGF-β, thereby permitting late-stage breast cancer cells to acquire invasive and metastatic phenotypes in response to TGF-β. Metastatic progression stimulated by TGF-β also relies on its ability to induce epithelial-mesenchymal transition (EMT) and the expansion of chemoresistant breast cancer stem cells. Precisely how this metamorphosis in TGF-β function comes about remains incompletely understood; however, recent findings indicate that the initiation of oncogenic TGF-β activity is contingent upon imbalances between its canonical and noncanonical signaling systems. Here we review the molecular and cellular contributions of noncanonical TGF-β effectors to mammary tumorigenesis and metastatic progression.     

相变高分子微球增效高强度聚焦超声消融裸鼠骨肉瘤

目的制备相变高分子微球,观察其增效高强度聚焦超声(HIFU)消融裸鼠骨肉瘤模型的效果。方法制备包裹液态氟碳的高分子微球,检测其形态、结构、粒径电位及相变条件;建立裸鼠骨肉瘤模型,随机分为空白组(不予处理)、对照组(注射生理盐水)和实验组1、2、3(注射稀释倍数分别为5、10、20倍的Pct-MP溶液),处理后立即用海级星对肿瘤进行辐照。于辐照后即刻和72h提取标本并观察坏死面积、行HE染色,并对72h提取的标本的坏死周边组织进行细胞增殖和凋亡测定。结果成功制备相变高分子微球;HIFU辐照后即刻提取的标本,实验组1、2的坏死面积与对照组差异均有统计学意义(P均0.05),但与实验组3的差异无统计学意义(P0.05);72h后提取的标本,实验组1、2的坏死面积进一步扩大、与辐照后即刻提取的标本的差异有统计学意义(P均0.05)。HIFU辐照72h后,实验组1、2、3与对照组间坏死周边组织的凋亡和增殖指数差异均有统计学意义(P均0.05)。结论在骨肉瘤裸鼠模型中,自制相变高分子微球能够增强HIFU对于骨肉瘤的消融效果,增强作用与微球浓度有关。     

α1,2Fucosylation Is a Superior Predictor of Postoperative Prognosis for Colorectal Cancer Compared with Blood Group A,B, or Sialyl Lewis X Antigen Generated within Colorectal Tumor Tissues

Background We have previously demonstrated tumor-specific α1,2fucosylation, which is associated with resistance of tumor cells to anticancer treatment in human colorectal tumor tissues. By using the YB-2 monoclonal antibody, the resulting products have been identified as Y, Le^b, and H type 2 antigens in colorectal tumor tissues. Methods Immunohistochemical analyses of colorectal cancer tissues (74 specimens) were performed with a newly established mouse monoclonal antibody, YB-3 specifically recognizing H disaccharide (Fucα1,2Galβ) structures, and anti-A, anti-B, YB-2, and anti–sialyl Lewis X (SLX) antibodies, together with the analyses of glycosyltransferases involved in the synthesis of ABH antigens in the same tissues. Results The YB-3 antibody enabled us to detect colorectal tumors, particularly tumors in the distal large intestine and the rectum, with high sensitivity (74.3%) and specificity (100%). From immunohistochemical and enzymatic analyses of colorectal tissues, we found that once α1,2fucosylation had proceeded in tumor tissues, blood group A or B antigen was also synthesized in approximately half of the tissues of A or B blood type, but not in their normal tissues. A correlation of survival rate with immunostaining of tissues was found only by YB-3 antibody and not by anti-A, anti-B, or anti-SLX antibody. Conclusions As a predictor of postoperative prognosis of patients with colorectal cancer, immunodetection of α1,2fucosylated antigens with the YB-3 antibody seemed to be superior to blood groups A, B, or SLX antigen in colorectal tumor tissues.     

Radiofrequency ablation of breast cancer: first report of an emerging technology.

HYPOTHESIS: Radiofrequency (RF) energy applied to breast cancers will result in cancer cell death. DESIGN: Prospective nonrandomized interventional trial. SETTING: A university hospital tertiary care center. PATIENTS: Five women with locally advanced invasive breast cancer, aged 38 to 66 years, who were undergoing surgical resection of their tumor. One patient underwent preoperative chemotherapy and radiation therapy, 3 patients received preoperative chemotherapy, and 1 had no preoperative therapy. All patients completed the study. INTERVENTIONS: While patients were under general anesthesia and just before surgical resection, a 15-gauge insulated multiple-needle electrode was inserted into the tumor under sonographic guidance. Radiofrequency energy was applied at a low power by a preset protocol for a period of up to 30 minutes. Only a portion of the tumor was treated to evaluate the zone of RF ablation and the margin between ablated and nonablated tissue. Immediately after RF ablation, the tumor was surgically resected (4 mastectomies, 1 lumpectomy). Pathologic analysis included hematoxylin-eosin staining and enzyme histochemical analysis of cell viability with nicotinamide adenine dinucleotide-diaphorase (NADH-diaphorase) staining of snap-frozen tissue to assess immediate cell death. MAIN OUTCOME MEASURE: Cancer cell death as visualized on hematoxylin-eosin-stained paraffin section and NADH-diaphorase cell viability stains. RESULTS: There was evidence of cell death in all patients. Hematoxylin-eosin staining showed complete cell death in 2 patients. In 3 patients there was a heterogeneous pattern of necrotic and normal-appearing cells within the ablated tissue. The ablated zone extended around the RF electrode for a diameter of 0.8 to 1.8 cm. NADH-diaphorase cell viability stains of the ablated tissue showed complete cell death in 4 patients. The fifth patient had a single focus of viable cells (<1 mm) partially lining a cyst. There were no perioperative complications related to RF ablation. CONCLUSIONS: Intraoperative RF ablation results in invasive breast cancer cell death. Based on this initial report of the use of RF ablation in breast cancer, this technique merits further investigation as a percutaneous minimally invasive modality for the local treatment of breast cancer.