Prospective study to assess the clinical efficacy of bone scintigraphy--some analyses of clinical data

The value of preoperative bone scans in patients with primary breast and prostate cancer was evaluated prospectively. Of 414 patients with breast cancer, clinical stage I is 14, II is 219, IIIA is 59, IIIB is 39 and IV is 14. Of 88 patients with prostate cancer, clinical stage I is 14, II is 15, III is 18 and IV is 41. 11 percent of patients with breast cancer and 54 percent of patients with prostate cancer had bone metastases. Clavicle, ribs, thoracic spine, lumbar spine and pelvis metastasized most frequently. The incidences of bone metastases were 18.4% with Scirrhous carcinoma, 15.4% with Medullary tubular carcinoma and 3.8% with Papillotubular carcinoma. The methodology and results of ROC analysis were described in our other papers. Some results of data analysis were described in this paper.     

Prospective study to assess the clinical efficacy of bone scintigraphy--ROC analysis

The value of preoperative bone scans in patients with primaly breast and prostate cancer was evaluated prospectively. The methodology and some clinical results were described previously. The clinical efficacy of the bone scan was assessed by using ROC analysis and we obtained the following results. 1) Preoperative bone scan of carcinomas of the breast is effective for patients with clinical stage IIIA, IIIB and IV. It is not so effective for patients with clinical stage I and II, but there is no denying the importance of it, because it provides a base-line scan for comparison to subsequent scans obtained in the postoperative period. 2) Preoperative bone scan of prostate carcinomas is effective, especially for clavicle, the ribs and the cervical spine, when compared with bone X-ray. 3) Bone scan is effective means for patients who were diagnosed uncertainly to have bone metastasis.     

Recent advances in the targeted fluorescent probes for the detection of metastatic bone cancer

Tumors of the breast, prostate, and lung are most likely to metastasize to the bone and typically indicates a poor cure and survival rate in cancer patients. Detection of metastatic bone cancer in early stage would save many lives and greatly improve patients' quality of life. Clinically, bone scintigraphy is often utilized to visualize bone metastases due to its relatively low cost and high sensitivity. Recently, a growth number of analytical researches aimed at developing targeted fluorescent probes to noninvasively image bone metastases with improved spatial resolution and specificity has been reported. In this review, we will summarize and discuss the recent published fluorescent probes on the accurate detection of metastatic bone cancer. First, the design principles of various targeted probes for imaging bone metastases will be presented, highlighting the signal moieties, targeting ligands, and physicochemical properties of the bone-specific probes. Next, the up-to-date bone-targeting fluorescent probes will be summarized and overviewed. Finally, future perspectives and challenges confronting the researchers in this field will be discussed.We believe this review will encourage novel ideas to develop smart targeted molecular probes for bone metastasis imaging,image-guided surgery, and therapeutic imaging materials.     

Progress in Targeted Alpha-Particle-Emitting Radiopharmaceuticals as Treatments for Prostate Cancer Patients with Bone Metastases

Bone metastasis remains a major cause of death in cancer patients, and current therapies for bone metastatic disease are mainly palliative. Bone metastases arise after cancer cells have colonized the bone and co-opted the normal bone remodeling process. In addition to bone-targeted therapies (e.g., bisphosphonate and denosumab), hormone therapy, chemotherapy, external beam radiation therapy, and surgical intervention, attempts have been made to use systemic radiotherapy as a means of delivering cytocidal radiation to every bone metastatic lesion. Initially, several bone-seeking beta-minus-particle-emitting radiopharmaceuticals were incorporated into the treatment for bone metastases, but they failed to extend the overall survival in patients. However, recent clinical trials indicate that radium-223 dichloride (²²³RaCl₂), an alpha-particle-emitting radiopharmaceutical, improves the overall survival of prostate cancer patients with bone metastases. This success has renewed interest in targeted alpha-particle therapy development for visceral and bone metastasis. This review will discuss (i) the biology of bone metastasis, especially focusing on the vicious cycle of bone metastasis, (ii) how bone remodeling has been exploited to administer systemic radiotherapies, and (iii) targeted radiotherapy development and progress in the development of targeted alpha-particle therapy for the treatment of prostate cancer bone metastasis.     

Glycoprotein synthesis as a function of epithelial cell arrangement: biosynthesis and release of glycoproteins by human breast and prostate cells in organ culture.

We demonstrate that a technique is available to investigate glycoprotein synthesis in organ cultures of human breast and prostate surgical specimens where the 3-dimensional epithelial cell arrangement remains intact. Malignant breast and prostate epithelium maintained their capacity to synthesize glycoproteins for at least 3 days as followed by the incorporation of [3H]glucosamine into macromolecules. Over 70% of incorporation was by malignant cells as judged by autoradiography. Labeled glycoproteins were released into glandular lumina and consequently into the culture fluid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed predominantly one group of macrmolecules released with an apparent molecular weight of 48,000 +/- 6,000 daltons. This glycoprotein was found in all of the breast specimens studied, which included 1 medullary, 1 infiltrating lobular, and 8 infiltrating duct carcinomas. The pattern was independent of the availability of estrogen receptors. A similar glycoprotein was also observed in the culture media from a Grade I and a Grade II well-differentiated infiltrating prostate carcinoma. Incorporation was below the level of detection in 4 of 6 cases of benign prostatic hyperplasia. A more complex pattern of labeled glycoproteins was found in the media of a Grade II and a Grade III poorly-differentiated prostate carcinoma. The established human mammary carcinoma cell line MCF-7 synthesized and released a similar 48,000 molecular weight glycoprotein but additional components with larger molecular weights were also released. An intriguing interpretation that 3-dimensional tissue integrity restricts some glycoprotein synthesis is discussed. Cells grown in 2-dimensional monolayers could escape from such a topographic restriction and express additional families of glycoproteins.     

Clinical significance of 99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) in the diagnosis of intrahepatic masses

Hepatobiliary scintigraphy with 99mTc-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) was carried out on 48 patients with intrahepatic masses, 44 with hepatocellular carcinoma and one each of hepatocellular adenoma, focal nodular hyperplasia, cholangiocellular carcinoma, and adenoid cystic carcinoma. Scans were performed twice, early scan (30 min post i.v.) and delayed scan (2.5 h post i.v.), and the delayed scan was used for assessing the accumulation of 99mTc-PMT in the intrahepatic masses. In the hepatocellular carcinoma group, based on individual patients, 17 out of 44 (38.6%) showed accumulation of 99mTc-PMT in various degrees; and based on individual masses, accumulation was noted in 21 out of 55 masses (38.2%). However, only the cases which had not received transarterial infusion of anti-cancer drugs (TAI) and/or blocking agents (TAE) were taken into consideration, 9 out of 18 patients (50%) and 12 out of 25 masses (48.0%) were found capable of picking up 99mTc-PMT. A case of hepatocellular adenoma showed a strong accumulation of 99mTc-PMT in the mass which was depicted as a defect on the 99mTc-colloid scan and did not show a significant accumulation of 67Ga. In a case of focal nodular hyperplasia, there were two space-occupying lesions (SOLs), one of which showed a clear-cut defect on the 99mTc-colloid scan and the other which showed only a distorted uptake pattern. However, both masses were strongly positive with 99mTc-PMT. 99mTc-PMT scintigraphy is useful in connection with 99mTc-colloid scan and sometimes with 67Ga-citrate in the diagnosis of intrahepatic masses originating from hepatocytes.     

MR-DWI成像预测乳腺癌腋窝淋巴转移的价值

本研究探讨磁共振弥散加权成像(MR-DWI)评估乳腺癌患者腋窝淋巴结转移的价值。回顾性选取乳腺癌患者68例(观察组),同时选取乳腺良性病变患者60例作为对照组,比较两组MR-DWI差异。观察组弥漫高信号、混杂高信号比例明显高于对照组(P<0.05);观察组病灶ADC值明显低于对照组(P<0.05);观察组Ⅲ期病灶ADC值明显低于Ⅰ~Ⅱ期(P<0.05);观察组腋窝淋巴结转移ADC值明显低于无淋巴结转移(P<0.05);弥漫高信号和其他信号组织ADC值比较差异无统计学意义(P>0.05);ADC值预测腋窝淋巴结转移的ROC曲线下面积为0.752,P<0.05。MR-DWI在乳腺癌腋窝淋巴结转移诊断应用价值较好,值得临床使用。     

Diagnostic value of female genital malignant tumors by using 111In-bleomycin scintigraphy.

In order to know if it is possible to objectively decide the extent of infiltration of female genital malignant tumors into parametrium by using 111In-bleomycin scintigraphy, a fundamental and clinical investigation was made. The result was as follows; 1) The radiochemical purity and stability of 111In-BLM were comparatively unchangeable. When this complex was kept at room temperature for a week, there was not more than 2% of the free 111In. 2) As to blood clearance, when the blood radioactivity of 111In-BLM 5 minutes after the injection was counted as 100%, about 80% of the radioactivity was cleared from the blood in 48 hours. Over 50% of the radioactivity was excreted into the urine in 48 hours. 3) Of 29 cases of female genital malignant tumors, 23 cases (79%) showed positive images. Therefore 111In-BLM was found to be one of the suitable radiopharmaceuticals for the diagnosis of female genital malignant tumors. 4) 111In-BLM scintigraphy was of great use for deciding the extent of the invasion of carcinoma cervicis uteri into parametrium and for the search of metastasis.     

Towards a proteome signature for invasive ductal breast carcinoma derived from label-free nanoscale LC-MS protein expression profiling of tumorous and glandular tissue

As more and more alternative treatments become available for breast carcinoma, there is a need to stratify patients and individual molecular information seems to be suitable for this purpose. In this study, we applied label-free protein quantitation by nanoscale LC-MS and investigated whether this approach could be used for defining a proteome signature for invasive ductal breast carcinoma. Tissue samples from healthy breast and tumor were collected from three patients. Protein identifications were based on LC-MS peptide fragmentation data which were obtained simultaneously to the quantitative information. Hereby, an invasive ductal breast carcinoma proteome signature was generated which contains 60 protein entries. The on-column concentrations for osteoinductive factor, vimentin, GAP-DH, and NDKA are provided as examples. These proteins represent distinctive gene ontology groups of differentially expressed proteins and are discussed as risk markers for primary tumor pathogenesis. The developed methodology has been found well applicable in a clinical environment in which standard operating procedures can be kept; a prerequisite for the definition of molecular parameter sets that shall be capable for stratification of patients.     

乳腺癌术前灰阶超声与彩色多普勒超声联合应用对预后的预测价值

目的探究乳腺癌术前灰阶超声与彩色多普勒超声联合应用对预后的预测价值。方法选取温州医科大学附属第一医院2013年5月—2015年5月期间收治的乳腺癌患者83例,治疗前均行灰阶超声与彩色多普勒超声检查,分析患者超声检查结果、临床征象与术后随访2年期间患者预后的关系,从而分析术前灰阶超声与彩色多普勒超声联合应用对乳腺癌患者预后的预测价值。结果乳腺癌肿块边界清晰、边界不清晰、边界恶性晕的患者2年无瘤生存率依次降低,边界恶性晕与边界不清晰患者死亡率均显著高于边界清晰患者(P0.05);肿瘤≥2 cm患者2年无瘤生存率显著低于2 cm患者;淋巴结转移患者2年无瘤生存率显著低于无转移患者(P0.05);血流分级Ⅱ级患者2年无瘤生存率明显低于0级(P0.05),Ⅲ级患者2年无瘤生存率显著低于0级和Ⅰ级(P0.05)。结论乳腺癌患者术前联合应用灰阶超声与彩色多普勒超声检查可确定肿瘤边界、大小及淋巴转移等征象,其与患者无瘤生存率、死亡率等预后指标密切相关,可作为预测乳腺癌患者预后的重要方法。     

Usefulness of bone imaging in diagnosis of sternocostoclavicular hyperostosis

Sternocostoclavicular hyperostosis (SCCH) is a rare disease that is characterized by hyperostosis and soft tissue ossification between the clavicles and the anterior part of the upper ribs. There have been few published reports of 99mTc-MDP bone imaging findings in this disease. Thirty-three patients who were suspected to have SCCH were studied with 99mTc-MDP bone imaging. Bone images were abnormal in 31 (94%) of 33 patients. Chest radiographs were available in 30 patients, but negative in 14 (46%) of them. Bone imaging revealed also radionuclide accumulations in other bones such as the vertebrae, femur or sacroiliac joints in ten (14 sites) of 33 cases. Bone scintigraphy was useful in the diagnosis of sternoclavicular hyperostosis.     

New cytotoxic isoflavone from the root bark of Brosimum utile

A new isoflavone 5,7,4'-trihydroxy-3'-(3-hydroxy-3-methylbutyl)isoflavone (isowigtheone hydrate) (1), together with six known isoflavones 2-7 and (-)epicatechin, were isolated from the root barks of Brosimum utile. Their structures were established on the basis of spectroscopic evidence. The in vitro cytotoxic activity of the new compound 1 was evaluated against cell lines MCF7 (human breast carcinoma), PC3 (human prostate carcinoma), HT29 (human colon cancer) and human dermis fibroblasts.     

Electrophoretic fingerprint metallothionein analysis as a potential prostate cancer biomarker

Prostate-specific antigen (PSA) is a routinely used marker of prostate cancer; however, the cut-off values for unambiguous positive/negative prostate cancer diagnoses are not defined. Therefore, despite the best effort, certain percentage of misdiagnosed cases is being recorded every year. For this reason, search for more specific diagnostic markers is of great interest. In this study, systematic comparison of PSA and metallothionein (MT) levels in blood serum of 46 prostate cancer-diagnosed patients is presented. It is clearly demonstrated that PSA levels vary significantly and despite normal total PSA values in the range of 0 - 4?ng/mL were obtained in over 36.9% of cases, positive prostate cancer was diagnosed by biopsy. In contrary, MT levels were considerably elevated in all tested samples and no significant variations were observed. These results are indicating the potential of MT as an additional prostate cancer marker reducing, in combination with PSA, the probability of false positive/negative diagnosis. To increase the throughput of the screening, chip-based capillary electrophoresis was suggested as a rapid and effective method for the fingerprinting analysis of prostate cancer from diseased blood sera.     

Straightforward synthesis,antiproliferative screening,and density functional theory study of some pyrazolylpyrimidine derivatives

Tetrahydropyrimidinone derivative was synthesized through one-pot three components condensation of 1,3-diphenylpyrazole-4-carbaldehyde with pentan-2,4-dione and urea under Biginelli reaction conditions. The corresponding chloro- and hydrazino derivatives were synthesized and utilized for the construction of some valuable N-heterocycles encompassing both pyrazole and pyrimidine cores, such as triazolopyrimidine, tetrazolopyrimidine, pyrazole, and pyrazolone derivatives through condensation with nitrogen nucleophiles and carbon electrophiles. The antiproliferative activity evaluation of the synthesized compounds against four human carcinoma cell lines namely, liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT-116) cell lines revealed that some of them provided significant potency, as well as the density-functional theory (DFT) was studied. The permeability of various hydrophilic and hydrophobic synthesized compounds across both normal and cancer cells is confirmed via DFT simulation in which the much higher permeability through aquaporin channels revealed the selective cytotoxicity toward cancer cells.     

Scintigraphy in the small animals using a human gamma camera--evaluation of bone scintigraphy in the rat mandible and maxilla

In order to obtain clear scintigrams of small animals, some improvements were brought on a pinhole collimator. Then, using a human gamma camera with this collimator improved, bone scintigraphy was attempted in the rat mandible and maxilla, experimentally to examine the desirable conditions of scintigraphy. The most desirable bone scan images were obtained under the conditions that the pinhole was 1.5 mm in diameter, the distance between the collimator and the object was 0 cm, and the exposure was 400.     

Proteomic approach for purification of seminal plasma proteins involved in tumor proliferation

Human seminal plasma contains a large array of proteins required for the normal physiology and metabolism of spermatozoa. These are mainly secreted from prostate epithelium, testes, and seminal vesicles. Fortunately, many of these are found to be present at elevated concentration in seminal plasma and act as a biomarker of different carcinomas as their levels are also enhanced in serum and are found to be involved in tumor progression and metastasis apart from fertility. The proteins which were overexpressed in the seminal plasma of prostate carcinoma patients were identified by 2-DE and MALDI-TOF/MS. We have designed a strategy to purify these four proteins prostate specific antigen (PSA), prostatic acid phosphatase (PAP), Zinc alpha2-glycoprotein (ZAG), and progastricsin (PG), together in homogeneity by using simple chromatographic techniques. Acidic and basic fractions of human seminal plasma were separated by ion exchange chromatography and further purified by gel permeation chromatography. Our results form a new and valuable resource for those attempting structure-based drug designing for prostate and other cancers where the amount of proteins is required in plenty and in native form.     

Significance of renal high uptake in bone marrow scintigraphy with 111In-chloride

The significance of high renal uptake found in patients with hematological disease who underwent bone marrow scintigraphy with 111In-chloride was investigated. In patients with a high renal uptake, the uptake in bone marrow was low, suggesting a reflection of erythropoietic activity. The reversal relationship, however, was not necessarily present. With regard to correlation with iron metabolism, significantly higher uptake of serum Fe and lower UIBC were found among those with high renal uptake, suggesting that the level of free trans ferrin in the serum is largely involved in the high uptake in the kidney.     

高危良性前列腺增生的术式探讨

目的探讨经尿道前列腺剜除术与经尿道双极等离子前列腺电切术治疗高危良性前列腺增生的临床疗效。方法选取高危良性前列腺增生患者86例,随机分为实验组和对照组,两组患者分别应用经尿道前列腺剜除术、经尿道双极等离子前列腺电切术治疗,对比两组患者的手术效果。结果两组患者的临床疗效及不良反应均无明显差异(P>0.05),但实验组患者的手术时间、膀胱冲洗时间及住院时间均短于对照组,术中出血量少于对照组,差异有统计学意义(P<0.01)。结论经尿道前列腺剜除术与经尿道双极等离子前列腺电切术治疗高危良性前列腺增生均安全有效,但经尿道前列腺剜除术的手术时间、膀胱冲洗时间及住院时间更短,术中出血量更少。