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At least 19 recordsLinked to original sources

[Successful complete androgen blockade (CAB) therapy for prostatic cancer detected from multiple lung metastases: a case report].

Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.

Adenocarcinoma↗

Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses.

To test the efficacy of combined high-throughput analyses (HTA) in target gene identification, screening criteria were set using >fivefold difference by microarray and statistically significant changes (p<0.01) in SAGE and EST. Microarray analysis of two normal and seven breast cancer samples found 129 genes with >fivefold changes. Further SAGE and EST analyses of these genes identified four qualified genes, ERBB2, GATA3, AGR2, and ANXA1. Their expression pattern was validated by RT-PCR in both breast cell lines and tissue samples. Loss of ANXA1 in breast cancer was further confirmed at mRNA level by Human Breast Cancer Tissue Profiling Array and at protein level by immunohistochemical staining. This study demonstrated that combined HTA effectively narrowed the number of genes for further study, while retaining the sensitivity in identifying biologically important genes such as ERBB2 and ANXA1. A distinctive loss of ANXA1 in breast cancer suggests its involvement in maintaining normal breast biology.

Algorithms↗

A highly polymorphic CA repeat marker at the EBAG9/RCAS1 locus on 8q23 that detected frequent multiplication in breast cancer.

BACKGROUND: Cloning of CpG binding sites in the human genome initially identified EBAG9 (estrogen receptor-binding fragment-associated gene 9), an estrogen-responsive gene mapped to chromosome 8q23. Its product was later found to be identical to RCAS1 (receptor-binding cancer antigen expressed on SiSo cells 1). RCAS1 was recently described as a cancer-surface antigen, implicated in immune escape in a human uterine adenocarcinoma cell line, which turned out to be identical to the EBAG9 molecule. AIM: The study seeks to isolate a highly polymorphic dinucleotide repeat at this locus that detects frequent multiplication of the EBAG9/RCAS1 gene. SUBJECT AND METHODS: A fragment containing CA repeat was identified by Southern blotting of bacterial artificial chromosome (BAC) clone containing the EBAG9/RCAS1 gene digested by Hae III, Sau 3A or Rsa I with (GT)20 probe, subcloned and sequenced. RESULTS: We isolated a polymorphic dinucleotide (CA) repeat sequence from a genomic clone containing the EBAG9/RCAS1 gene located at 8q23. High heterozygosity (0.859) makes this polymorphism a useful marker in genetic studies. This marker detected frequent multiplication of the EBAG9/RCAS1 gene in primary breast cancers (27 of 129 tumours). CONCLUSION: This marker is useful for detecting frequent multiplication of the EBAG9/RCAS1 gene in primary breast cancers and other cancers.

Alleles↗

American Cancer Society--National Prostate Cancer Detection Project. Results from multiple examinations using transrectal ultrasound, digital rectal examination, and prostate specific antigen.

BACKGROUND: The American Cancer Society-National Prostate Cancer Detection Project is a prospective study of the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). Two thousand nine hundred ninety-nine men not previously suspected of having prostate cancer have been entered on study in ten participating clinical centers. METHODS: The study protocol requires these men to undergo testing with the three detection methods under investigation on an annual basis for up to 5 years. Data currently are available on 1972 men who have completed protocol requirements for two sequential series of examinations. RESULTS: At the first visit, it was recommended that 16.5% of subjects undergo biopsy based on the TRUS and/or DRE findings. Seventy-three (3.7%) men were found to have cancer after the first series of examinations. When the 1899 men who did not have cancer were reexamined, in 11.4%, a biopsy was recommended, and an additional 33 (1.7%) cancers were detected. Cancer detection rates were higher in older men, and the sensitivity of TRUS was higher than that of DRE at both examinations. The positive predictive values (PPV) of TRUS and DRE varied significantly depending on the PSA level; PPV decreased at the second examination. Positive findings during the second examination were associated with elevated PSA levels during the earlier visit and rising PSA levels between examinations. Analyses of the 106 cancers detected currently showed a preponderance of early-stage cancer and low Gleason scores. CONCLUSIONS: It may be possible to increase the early detection of prostate cancer by periodic examination by a combination of detection modalities.

Aged↗

[A case of multiple primary cancers, hepatoma and seminoma, detected by 67Ga citrate and 99mTc-HIDA scintigraphy].

A case of multiple primary cancers, hepatoma and seminoma, was detected by 67Ga citrate and 99mTc-HIDA scintigraphy. 67Ga citrate accumulated in the chest wall, the hepatic lesion and the testis. 99mTc-HIDA accumulated in the chest wall. Therefore we suspected that the chest wall lesion was a tumor metastasized from hepatocellular carcinoma and another cancer was present in the testis. After these examinations orchiectomy and needle biopsy were done. Pathologically, the testicular tumor was seminoma and hepatic and chest wall tumors were hepatocellular carcinoma (Edmondson-II).

Carcinoma, Hepatocellular↗

Multifocal transitional cell carcinoma of the bladder and upper urinary tract: molecular screening of clonal origin by characterizing CD44 alternative splicing patterns.

PURPOSE: CD44 is a widely expressed cell surface adhesion molecule in which various isoforms arise from alternative RNA splicing mechanism during cancer initiation. We assessed whether multifocal transitional cell carcinoma of the urothelium is due to field change and/or intraluminal seeding and implantation. MATERIALS AND METHODS: In a series of 24 patients with synchronous and/or metachronous multiple urothelial cancers we performed reverse transcription-polymerase chain reaction analysis using a set of primers capable of amplifying all CD44 splice variant isoforms. After polymerase chain reaction products were electrophoresed band intensities with areas corresponding to the major isoforms (that is CD44s, CD44v10 and CD44v8-10) were quantified, and CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios were calculated. Moreover, p53 gene mutations in exons 4 to 11 were screened by direct DNA sequencing. RESULTS: Of these 24 cases 18 showed similar CD44v10-to-CD44s and CD44v8-10-to-CD44s ratios in among multiple urothelial cancers in each case. However, in the remaining 6 cases these ratios were quite different among multiple cancer lesions. Furthermore, different types of p53 mutation were detected among multiple cancer lesions in only 2 of 24 cases, which also indicated different patterns of CD44 alternative splicing. CONCLUSIONS: These findings suggest that at least some multiple transitional cell carcinomas of the urothelium seem to be of independent origin based on the analysis of alternative RNA splicing of CD44. Moreover, this hypothesis was further supported by the evaluation of p53 gene mutation.

Alternative Splicing↗

Molecular strategy for detecting metastatic cancers with use of multiple tumor-specific MAGE-A genes.

BACKGROUND: The human melanoma-associated antigen family A (MAGE-A) has high specificity and expression in various malignancies, but individual family members are expressed at low frequency in any one particular type of cancer. We therefore developed a method to detect mRNAs from multiple MAGE-A genes in a single reaction. METHODS: Universal MAGE-A (uMAGE-A) primers and probe were designed to reverse-transcribe, amplify, and detect by electrochemiluminescence (ECL) MAGE-A mRNAs on the Origen Analyzer. The assay was performed on total RNA of melanoma (n = 9 cell lines and 24 tumors), breast cancer (n = 7 and 26), and colorectal cancer (CRC; n = 5 and 12). We also evaluated blood from melanoma (n = 50), breast cancer (n = 16), and CRC (n = 21) patients. RESULTS: The uMAGE-A mRNA was detectable in 0.01-1 ng of cell line RNA. The identity of the uMAGE-A cDNA products was confirmed by sequencing and polyacrylamide gel electrophoresis. The uMAGE-A assay increased detection of melanoma, breast cancer, and CRC tumor by 13%, 31%, and 25%, respectively, compared with a MAGE-A1 assay, and by 17%, 19%, and 25%, respectively, compared with a MAGE-A3 assay. The uMAGE-A assay detected circulating tumor cells in the blood of melanoma (24%), breast cancer (25%), and CRC (29%) patients. CONCLUSIONS: The uMAGE-A reverse transcription-PCR/ECL assay provides a practical and sensitive approach for detection of various metastatic cancers in tissues and blood.

Antigens, Neoplasm↗

Quantitative multiplex methylation-specific PCR assay for the detection of promoter hypermethylation in multiple genes in breast cancer.

If detected early, breast cancer is eminently curable. To detect breast cancer in samples with little cellularity, a high level of sensitivity is needed. Tumor-specific promoter hypermethylation has provided such a valuable tool for detection of cancer cells in biological samples. To accurately assess promoter hypermethylation for many genes simultaneously in small samples, we developed a novel method, quantitative multiplex-methylation-specific PCR (QM-MSP). QM-MSP is highly sensitive (1 in 10(4)-10(5) copies of DNA) and linear over 5 orders of magnitude. For RASSF1A, TWIST, Cyclin D2, and HIN1, we observed significant differences in both the degree (P < 0.003) and incidence (P < 0.02) of hypermethylation between normal and malignant breast tissues. Evaluation of the cumulative hypermethylation of the four genes within each sample revealed a high level of sensitivity (84%) and specificity (89%) of detection of methylation. We demonstrate the application of this technique for detecting hypermethylated RASSF1A, TWIST, Cyclin D2, HIN1, and RARB in 50-1000 epithelial cells collected from breast ducts during endoscopy or by lavage. Such an approach could be used in a variety of small samples derived from different tissues, with these or different biomarkers to enhance detection of malignancy.

Actins↗

Circulating microRNA panels for multi-cancer detection and gastric cancer screening: leveraging a network biology approach.

BACKGROUND: Screening tests, particularly liquid biopsy with circulating miRNAs, hold significant potential for non-invasive cancer detection before symptoms manifest. METHODS: This study aimed to identify biomarkers with high sensitivity and specificity for multiple and specific cancer screening. 972 Serum miRNA profiles were compared across thirteen cancer types and healthy individuals using weighted miRNA co-expression network analysis. To prioritize miRNAs, module membership measure and miRNA trait significance were employed. Subsequently, for specific cancer screening, gastric cancer was focused on, using a similar strategy and a further step of preservation analysis. Machine learning techniques were then applied to evaluate two distinct miRNA panels: one for multi-cancer screening and another for gastric cancer classification. RESULTS: The first panel (hsa-miR-8073, hsa-miR-614, hsa-miR-548ah-5p, hsa-miR-1258) achieved 96.1% accuracy, 96% specificity, and 98.6% sensitivity in multi-cancer screening. The second panel (hsa-miR-1228-5p, hsa-miR-1343-3p, hsa-miR-6765-5p, hsa-miR-6787-5p) showed promise in detecting gastric cancer with 87% accuracy, 90% specificity, and 89% sensitivity. CONCLUSIONS: Both panels exhibit potential for patient classification in diagnostic and prognostic applications, highlighting the significance of liquid biopsy in advancing cancer screening methodologies.

Neoplasms↗

Prostate cancer detection and tumor characteristics in men with multiple biopsy sessions.

PURPOSES: To address prostate cancer (PCa) detection with respect to the number of biopsy sessions performed, to identify risk factors for detection after a negative biopsy, and to analyze the clinical characteristics of the detected tumors. SCOPE: Only biopsied men (sextant) were included. A total of 1011 biopsy sessions were carried out in 770 men; 172 underwent a second prostate biopsy and 51 a third biopsy. During the first biopsy round, 111 cancers were found (14.4%), 27 in the second (15.7%), and five during the third round (9.8%), P=0.156. Only high-grade PIN or atypia were identified as independent predictors or PCa detection in subsequent biopsies (P=0.008). A nonsignificant increase of clinically localized tumors, and a decrease of metastatic and poorly differentiated cases were found when more biopsy sessions were needed for detection. CONCLUSIONS: A nonsignificant trend to lower cancer detection rates and less clinical relevance of the tumors detected can be observed when more biopsy rounds are needed for detection.

Adult↗

Early detection of prostate cancer following repeated examinations by multiple modalities: results of the American Cancer Society National Prostate Cancer Detection Project.

The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multicenter, interdisciplinary demonstration project to assess the impact on early detection of transrectal ultrasound (TRUS), prostate-specific antigen (PSA), and digital rectal examination (DRE). Preliminary data are available from the first 3-5 y of planned observation. The results show declining rates of detection for each succeeding examination. Cancer detection rates are highly dependent on age. The positive predictive value of a solitary examination is low regardless of modality, but any combination of positive results has a much better predictive value. The cancers detected were predominantly clinically localized tumors, and detection of advanced stage cancer was uncommon after the initial examination. Radical prostatectomy was the most common form of treatment. These findings have implications for prostate cancer early detection guidelines and practice.

Aged↗

[Multiple primary malignancies in patients with head and neck cancer].

From July, 1978 to December, 1985, 1,138 cases of malignancies of the head and neck were treated at the authors' hospital, and up to June, 1986, 132 patients with multiple primary malignancies were detected. In all cases, the incidence rate of a multiple primary malignancy was 11.6%. In 45 (33.0%) of these head and neck cancer cases, the multiple cancer was detected simultaneously, and as for the other cases (66.7%), they were discovered metachronously. In patients with a cancer of the mesopharynx, the incidence rate of a multiple primary malignancy was the highest (25.8%), whereas in those with a cancer of the parotid gland and in those with a cancer of the hypopharynx, the incidence rates were 20.0% and 14.9%, respectively. In most patients the second malignancy occurred in the same head and neck region, and in the rest, the second malignancy was a gastric cancer, a lung cancer, or an esophageal cancer in that descending order. Of the 45 synchronous cancer cases, ten were a thyroid cancer, most being latent. In head and neck malignancies, the authors stress the importance of a precise investigation prior to start of therapy and of maintaining follow-up investigations after therapy.

Adult↗

[Second primary malignant tumors in patients with primary renal cell carcinoma].

INTRODUCTION: Among multiple primary cancers in the same patient, renal cell carcinoma occurring either synchronously or metachronously is one of the most common. AIM: The aim of the study was to determine the frequency of second primary malignant tumor in patients with primary renal cell carcinoma. MATERIAL AND METHODS: Between 1992 and 2000, 447 patients underwent nephrectomy for primary renal tumor at the Department of Urology, Sestre milosrdnice University Hospital. Out of 447 patients 310 were registered at Cancer Registry of the Republic of Croatia. There were data on 297 patients with renal cell carcinoma, 197 male and 104 female patients, age group 24-91 (mean 59.9) years. RESULTS: Data on 24 (8.1%) patients with second primary malignant tumors were found in Hospital Registry and Croatian Cancer Registry during the study period. There were 13 male patients, age range 47-80 (median 65.1) years, and 11 female patients, age range 51-70 years (median 61.1) years with 26 second primary tumors. One male patient presented with four different primary tumors (kidney, prostate, urinary bladder and colon). The patients most commonly presented with prostate and colon carcinoma. The second malignant primary tumors occurred most commonly as antecedent to renal cell carcinoma, i.e. in 11 (42.3%) cases. CONCLUSION: Our results indicate that during the clinical follow-up of patients treated for primary renal cell cancer, a possibility of second primary cancers should always be considered. In order to upgrade detection of multiple cancer, the quality and completeness of cancer notification and registration from hospitals as well as collaboration between the National Cancer Registry and hospital cancer registries should be improved.

Adult↗

A clinicopathologic study on multiple gastric cancers with special reference to distal gastrectomy.

Simultaneous multiple gastric cancer was seen in 49 (5.8%) of 852 resected stomachs. Patients with multiple cancers were older than those with single gastric cancers (P less than 0.01) and the incidence of multiple gastric cancer was significantly higher in male patients than in female patients (P less than 0.05). The incidence rates of multiple carcinomas were 9.6% of early gastric carcinomas and 4.0% of advanced gastric carcinomas. With regard to histologic type, the incidence rate of the differentiated type was 71% and the incidence rate of the undifferentiated type was 29%. In 68 serially resected stomachs, 5 (7.4%) new multiple cancers were detected microscopically, whereas 4 (5.9%) had already been diagnosed grossly. The incidence rate of multiple carcinoma increased to 13.2% by this procedure. The cases that were cut serially showed that most of the multiple cancers were located distally from the F-line presenting the line along which intestinal metaplasia appeared. This study suggests that the surgeon is required to resect the area including the F-line at the time of distal gastrectomy so as not to leave another cancer in the gastric remnant.

Adult↗

A novel multiple FISH array for the detection of genetic aberrations in cancer.

Interphase multicolor fluorescence in situ hybridization (IM-FISH) has great promise for improving cancer diagnosis because it can directly visualize multiple changes in chromosomes and gene copy number on a cell-to-cell basis. However, no more than four targets can be detected simultaneously by current commercially available IM-FISH protocols, and the DNA probes used are too large to detect the single-gene aberrations that characterize tumorigenesis. As a result, multiple FISH has a low sensitivity in detecting cancer cells. To overcome such limitations, we first developed specific genomic probes for the genes relevant to primary lung cancer. We next designed a multiple FISH array by arranging four different compositions of cocktails of four probes for each gene on a coverslip, which allowed four four-color FISH experiments to be performed in parallel on a single slide. We then tested the multiple FISH array on bronchial brushing samples from lung cancer patients to determine its ability to detect genetic abnormalities. A comparison of the data with the results of cytology and commercial four-color FISH suggested that the multiple FISH array had the highest sensitivity for cancer detection. The technique may thus be a powerful laboratory strategy for cancer prevention and early detection and for improved patient management.

Bronchoalveolar Lavage Fluid↗

[Subareolar injection of 99m-Tc sulfur colloid for sentinel nodes identification in multifocal invasive breast cancer].

The objective were to study the relevance of the subareolar injection for sentinel node [SN] detection in multiple foci breast cancer. Seventy-nine patients with infiltrative breast carcinoma (diagnosed pre-operatively by core biopsy) and a mean age of 55 (31-78) years were enrolled. All patients were free of previous homolateral surgery, chemotherapy, locoregional radiotherapy or prevalent axillary lymph node. Using four 0.1 ml injections of 1.8 MBq, the technetium-99m 100 nm filtered sulfur colloid was injected by subareolar way (group I) in 16 cases of radiologically cancer with multiple invasive foci and 31 cases of radiologically unifocal cancer, and by peritumoral way (group II) in 32 cases of radiologically unifocal cancer. Scintigrams were obtained 2 to 4 hours after the injections and radioactive nodes were detected peroperatively 18 hours after the injection by intraoperative detection probe. Individual removal of all radioactive nodes was followed by axillary dissection at levels I and II of Berg including Rotter area control. All sentinel nodes were submitted to standard histopathological analysis on serial sections at 500 mu intervals completed by immunohistochemistry for cytokeratin on negative SN. SN were detected by scintigrams in 85% and 88% of the cases of group I and group II respectively, but in 98% and 97% of the cases of respectively both groups by intraoperative probe. Group I was composed of 69% ductal, 22% lobular and 9% tubular carcinomas, and group II of 87% ductal, 10% lobular and 3% tubular carcinomas. Seven and 5 radiologically unifocal tumors were in fact with multiple invasive foci at histology in groups I and II respectively. The complete scintigraphic procedure permitted the detection of a mean number of 2.7 (1-7) SN in group I and 2.3 (1-4) in group II (NS). In group I, the SN were metastatic in 22 patients (48%), 15 of them with the metastases being restricted to the SN, whereas in group II, the SN were metastatic in 9 patients (28%), 5 of them with the positivity restricted to the SN. No false negative result (SN negative and other axillary nodes positive) was observed in group I and only one false negative result in group II which was related to a cancer with histological multiple invasive foci. Sensitivities were 100% and 90%, and negative predictive values were 100% and 95%, for groups I and II respectively. Subareolar injection of radiocolloid allows identification of SN in cases of unifocal and multiple cancer. The mean number of SN detected by the subareolar method is not significantly different, although higher, to that detected by peritumoral injection.

Adenocarcinoma↗

Simultaneous multiple early cancers of esophagus and stomach treated by endoscopic mucosal resection.

Endoscopic mucosal resection (EMR) has been accepted as a completely curative treatment of gastrointestinal mucosal cancers. With advances in diagnostic techniques, the tendency to detect simultaneous multiple primary cancers is increasing. Patients with another cancer coexisting with esophageal cancer have had a poor prognosis, but if both cancers are detected in the early stage, complete treatment consisting only of endoscopic surgery, with a good prognosis, is expected. We describe two cases of simultaneous multiple early cancers of the stomach and esophagus, treated by EMR.

Adenocarcinoma↗

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗