tbuckley/cabot-search huggingface dataset:
TGFBR3 is lost in prostate cancer, contributing to malignant transformation
Authors: N. Sharifi, E. Hurt, W. L. Farrar
Journal: Journal of Clinical Oncology (2006)

14552 Background: Resistance to transforming growth factor-beta (TGF-beta) is common in solid tumors. Alterations of TGF-beta biology in prostate cancer are complex, with a downregulation of this cytokine reported in early disease and upregulation of TGF-beta in advanced disease. Mechanisms of TGF-beta resistance in early disease are not well understood. We have investigated the function of TGF-beta receptor 3 (TGFBR3) to determine its role in prostate cancer. Methods: We undertook an analysis of the data in seven published DNA microarray studies of nonneoplastic prostate tissue versus prostate cancer specimens using oncomine. Of the genes we identified as known to be directly involved in the TGF-beta pathway, loss of TGFBR3 was most significantly associated with prostate cancer. We determined TGFBR3 expression in prostate cancer cell lines and the immortalized prostate epithelial cell line RWPE-1. To assess the consequences of loss of TGFBR3 expression, we created an shRNA construct and stably infected RWPE-1 cells. We analyzed gene expression changes by DNA microarray analysis and confirmed changes by Western Blot. We then searched TGFBR3 regulated genes based on our knockdown studies in the data set from the seven previously published studies. Furthermore, we evaluated the phenotypic consequences of TGFBR3 knockdown. Results: TGFBR3 expression was significantly lost in 6 of 7 microarray studies. TGFBR3 was downregulated in 3 of 4 of prostate cancer cell lines, compared with RWPE-1. DNA microarray analysis of TGFBR3 knockdown in RWPE-1 cells showed that expression of DPYSL3, Vimentin, COCH, SERPINF1, PMP22, LTBP1 and BMP4 were decreased both with TGFBR3 knockdown and in the transition to prostate cancer. Of these genes, vimentin expression was most dramatically downregulated in TGFBR3 knockdown cells and we showed that vimentin protein expression was completely lost. The phenotypic consequence of TGFBR3 knockdown in RWPE-1 cells was formation of colonies that appear to reflect loss of contact inhibition. Conclusions: TGFBR3 is lost in prostate cancer. TGFBR3 knockdown leads to colony formation by immortalized prostate epithelial cells. Our data suggests that loss of TGFBR3 contributes to malignant transformation of the prostate. No significant financial relationships to disclose.
Hepatocellular Carcinoma: Prognosis Using Hepatoma-Derived Growth Factor Immunohistochemistry
Authors: Hideji Nakamura, Kenya Yoshida, Yasuhiko Tomita
Journal: Liver Cancer (2009)

Hepatoma-derived growth factor (HDGF) is a heparin-binding protein purified from the conditioned medium of the human well-differentiated hepatocellular carcinoma (HCC) cell line, HuH-7, which can proliferate autonomously in a serum-free chemically-defined medium; this factor is highly expressed in several cancer cells (Nakamura et al., 1989, 1994; Mori et al., 2004). Hepatoma-derived growth factor is an acidic 26 kDa protein consisting of 230 amino acids with no hydrophobic signal sequence in its N-terminus, and it has a high affinity to the glycosaminoglycans heparin and heparan sulphate (Nakamura et al., 1994; Dietz et al., 2002). Exogenously supplied HDGF stimulates the proliferation of fibroblasts, endothelial cells, vascular smooth muscle cells, pulmonary epithelial cells and hepatocytes, as well as HCC, lung cancer, and colon cancer cells. A possible receptor-binding site is estimated to be residing at amino acid residues 81–100 within the hath region (described below) (Abouzied et al., 2005). Indeed, exogenous HDGF stimulates the Erk phosphorylation in endothelial cells (Everett et al., 2004).Hepatoma-derived growth factor is a major member of the HDGF family of proteins which consists of HDGF and five HDGF-related proteins (HRP) (Izumoto et al., 1997; Dietz et al., 2002). The N-terminal region of HDGF is highly conserved among the other five HDGF-related proteins (HRP), and this region is called hath (homologous to the amino terminus of HDGF) region, which contains the PWWP domain (Izumoto et al., 1997). The HDGF family members are characterized based on whether they contain the hath region and nuclear localization signals (NLS) in their gene-specific regions and are targeting to the nucleus (Nakamura and Hada, 2004). Hepatoma-derived growth factor contains two nuclear localization signals (NLS) in the molecule of HDGF; the first functional nuclear localization signal (NLS1) is in the hath region and the second NLS (NLS2) is in gene-specific regions of the C-terminal region (Kishima et al., 2002a). Hepatoma-derived growth factor can traffic to the nucleus using these NLSs, especially the NLS2 in its gene-specific region, and this factor is dominantly localized in the nucleus rather than in the cytoplasm (Everett et al., 2001). The gene-specific region of HDGF, at least the bipartite NLS sequence and both the N-and C-terminal neighboring portions, is essential for the mitogenic activity (Kishima et al., 2002a). Thus, HDGF exerts its proliferating activity via two different pathways: (1) via a putative plasma membrane-located HDGF receptor for which signaling depends on the hath region, resulting in MAP kinase activation, and (2) via targeting to the nucleus by NLS.
Hereditary breast/ovarian cancer families: The impact of mutation prediction models on BRCA1/2 mutation screening costs
Authors: C. Capalbo, E. Ricevuto, P. Marchetti, B. Adamo, V. Adamo, A. Vestri, L. Frati, I. Screpanti, A. Gulino, G. Giannini
Journal: Journal of Clinical Oncology (2006)

20027 Background: The considerably high costs of BRCA1/2 mutation screening together with the expanding request for inherited breast/ovarian cancer genetic counselling and testing, dictates the need for more accurate selection of the appropriate candidates for analysis. The aim of the present study was to evaluate, the impact that careful selection of appropriate candidates by means of BRCAPRO, Myriad tables and IC software prediction models might exert on reduction of societal costs. Methods: 86 unrelated high risk breast/ovarian cancer families were selected for mutation screening; BRCA1/2 entire coding sequences and each intron/exon boundary were screened by direct sequencing (PTT limited to BRCA1 exon 11). The a priori probability of carrying a pathologic BRCA1/2 germline mutation was calculated by either BRCAPRO or IC software (country-customized versions of BRCAPRO), or by the Myriad prevalence mutation tables (2004). We classified our index cases as “carrier-positive” when their carrier probability exceeds 10%. According to recent literature, our analysis assumed a cost of $1,713 for genes sequencing of each proband. Results: We observed 19 pathogenic germline mutations with an overall detection rate of 22.1%. IC software and Myriad tables were more efficient in predicting mutated cases, showing higher sensitivity (95% and 84%, respectively) and a better negative predictive value (NPV, 96% and 91%, respectively) compared to BRCAPRO (sensitivity 74% and NPV 87%). Particularly, the IC software misclassified a pathogenic mutation carrier in only one case. The costs afforded for genetic testing on the whole sample was $147,318. The family selection assisted by the IC software, BRCAPRO, Myriad tables could result in a total cost of $104,493, $78,798 and $90,789, respectively. Even maintaining high accuracy in carrier status prediction, the country-customized version of BRCAPRO imparted more than 30% cost reduction. Conclusions: Considering a balance between economical advantages and the different performances in mutated status prediction, our analysis suggest that the country-customized versions of BRCAPRO and Myriad Tables allow efficient selection of candidates for BRCA1/2 mutation analysis and a significant impact on societal costs. No significant financial relationships to disclose.
The clinical significance of thymidylate synthase (TS) expression in primary colorectal cancer: An Intergroup combined analysis
Authors: P. G. Johnston, A. Benson, P. Catalano, S. Eapen, N. Wolmark, D. Sargent, U. Mc Dermott, L. Colangelo, S. Wieand, R. Goldberg, C. Allegra
Journal: Journal of Clinical Oncology (2005)

3510 Background: Thymidylate synthase (TS) catalyses the methylation of dUMP to dTMP required for DNA synthesis and repair. TS is also a target for fluoropyrimidines such as 5-FU. Several studies have suggested that TS is a prognostic and predictive marker in fluoropyrimidine-based chemotherapy in colorectal cancer (CRC). The purpose of this Intergroup combined analysis was to evaluate the prognostic significance of TS expression in primary CRC and the role of TS as a predictor of response to adjuvant 5-FU by pooling data from a large number of studies. Methods: TS expression was assessed by immunohistochemistry on tumors from 1326 patients with stage II and III CRC enrolled in 11 trials evaluating 5-FU-based adjuvant chemotherapy. TS intensity levels 0–1 were considered low intensity, TS levels 2–3 were considered high intensity staining. The trials are from the ECOG, NSABP and NCCTG co-operative groups and evaluated a variety of 5-FU-based regimens including 5-FU/LV, 5-FU/LEV and PVI 5-FU compared to surgery or observation. Results: Seventy-nine percent of tumors were classified as high TS expression. Only age and race were independent prognostic factors for overall survival in the stage II patients (p=0.0005 and 0.0037 respectively). For stage III patients age (p=0.0004), gender (p=0.0038), race (p=0.0022) and 5-FU treatment (p=0.0028) and TS expression (p=0.0098) were all independent prognostic factors for overall survival. A proportional hazards regression model of low/high TS score and 5-FU treatment for stage III and stage IIIC revealed a significant interaction between TS and 5-FU treatment effect for stage IIIC patients (p=0.0459). Univariate covariate regression models of stage IIIC patients demonstrated that only those patients with low TS expression derived significant benefit from 5-FU therapy (p=0.0059). Conclusions: This analysis suggests that TS is not a predictor of 5-FU response in the adjuvant setting. However it remains a statistically valid independent prognostic factor for overall survival in stage III patients. Stage IIIC tumors would appear to behave differently from stage III tumors overall, and TS is predictive of 5-FU benefit in this subgroup. No significant financial relationships to disclose.
GW26-e1438 Ginsenoside Rb1 Reverses Human Umbilical Vein Endothelial Cells Senescence Induced by Hydrogen Peroxide
Authors: Bin Zhou, Liangying Lin, Shujie Yu, Zhenda Zheng, Lin Wu, Yong Liu, Baoshun Hao, Zhiming Song, Lin Chen, Xiaoxian Qian
Journal: Journal of the American College of Cardiology (2015)
Premalignant Lesions of the Cervix in Women of Cali, Colombia&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: E Duque, C Cuello, N Aristizábal, W Haenszel, S Botero, P Correa
Journal: JNCI Journal of the National Cancer Institute (1979)

A detailed histologic study was made of uterine cervices from 441 autopsy specimens from the population of Cali, Colombia. Women in this city have one of the highest registered incidence rates of cancer of the uterine cervix. The following prevalence (in percent) of lesions in adult women was found: cervicitis, 79; reserve cell hyperplasia, 14; squamous metaplasia, 41; dysplasia, 9. Contrary to expectations, no increase in prevalence of these lesions was found with age, lower socioeconomic status, or number of pregnancies. A similar study of a sample of hysterectomies performed for uterine prolapse showed approximately the same results. The findings suggest that promotional factors are more important than initiator factors in uterine cervical carcinogenesis.
A phase II study of paclitaxel and vinorelbine (Pacl-Vin) in hormone-refractory metastatic prostate cancer (HRPC): Double tubulin targeting
Authors: S. Sewak, S. Kosmider, V. Ganju, A. Woollett, B. Le, E. Yeow, M. Henry, R. Bell
Journal: Journal of Clinical Oncology (2006)

14559 Background: Phase 2 trials of Paclitaxel+corticosteroid or Vinorelbine+corticosteroid have shown 20–40% PSA responses. Preclinical models have shown synergy between Paclitaxel and Vinorelbine. A phase I trial showed this to be a tolerable combination. Methods: The aim of this study was to determine the efficacy and safety of Paclitaxel and Vinorelbine. 30 castrate pts with progressive, metastatic prostate cancer were enrolled. Previous radiotherapy, strontium therapy, 1 line of chemotherapy, and concurrent bisphosphonate therapy were allowed. Pts were treated with Paclitaxel 40 mg/m 2 (1 hr), and Vinorelbine 20 mg/m 2 iv on day-1 &amp; day-8 of a 21-day cycle. All pts received standard premedication for Paclitaxel including dexamethasone. Results: Baseline pt characteristics were: median ECOG PS of 1 (range 0–2), median age 71, mean PSA 413ng/mL, mean Hb 11.9 g/dL. For 10 pts with measurable disease the partial response rate was 20%, with 70% of pts achieving stable disease (SD). Of 23 assessable pts, 9% had 50% decline in PSA, and 78% had SD, maintained for at least 4 weeks. Median overall survival was 7.3 months. Median progression free survival was 3.3 months. All pts completed quality of life (QOL) questionnaires. There was an improvement over baseline after 3 cycles of therapy in pts pain, appetite, constipation, voiding and overall wellbeing (p = non-significant). Grade 3/4 toxicities were: anemia 3%, neutropenia 8%, infection 2%, febrile neutropenia 4%, lethargy 1%, and somnolescence 1%. 1 pt died as a result of sepsis and neutropenia. Conclusions: In this poor prognostic cohort of pts the combination of Paclitaxel and Vinorelbine is a tolerable regimen, which has demonstrated minor PSA response, with the majority of pts achieving PSA stability. There was some objective response to this regimen and importantly it stabilized disease in a majority of pts. Important QOL parameters such as pain were improved.This is a useful regimen to test in poor prognosis HRPC pts. No significant financial relationships to disclose.
Transarterial chemoembolization using drug eluting beads for the treatment of hepatocellular carcinoma: Now and future
Authors: Hyun Young Woo, Jeong Heo
Journal: Clinical and Molecular Hepatology (2015)

Transarterial chemoembolization (TACE) using doxorubicin-eluting beads (DEBs) have been introduced as a novel device which ensures more sustained and tumor-selective drug delivery and permanent embolization compared to conventional TACE with lipiodol. Studies highlighting the use of TACE with DEBs for the treatment of hepatocellular carcinoma (HCC) have shown similar or better results compared to conventional TACE with lipiodol. TACE with DEBs is increasingly being performed interchangeably with conventional TACE. This review assessed the characteristics, clinical outcomes and future direction of TACE with DEBs compared to conventional TACE. Keywords: Drug eluting beads; Hepatocellular carcinoma; Transarterial chemoembolization
Transformation of Rodent Cells by Adenovirus 19 and Other Group D Adenoviruses&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R M McAllister, M O Nicolson, G Reed, J Kern, R V Gilden, R J Huebner
Journal: JNCI Journal of the National Cancer Institute (1969)

Primary rat-embryo cells and NIL-2 hamster cells were transformed by adenovirus (Ad) types 9, 10, 13, 15, 17, 19, and 26. The transformed cells formed multilayered foci in monolayer cultures. Cell lines derived from such foci formed colonies when suspended in soft agar medium. Approximately 2.7 × 104 plaque-forming units (PFU) of Ad-19 were required to induce one focus of transformed rat cells. The highest transformation rates obtained were 0.01% for rat cells exposed to about 14 PFU/cell. In hamsters, Ad-19 and Ad-26 transformed NIL-2 cells formed tumors with the morphological characteristics of adenovirus tumors. Histologically, cell colonies of Ad-19 transformed cells also resembled adenovirus tumors. Complement fixation tests using sera from hamsters bearing tumors induced by Ad-19 or Ad-26 transformed NIL-2 cells indicate that the transformed cells shared a common T antigen with all members of adenovirus hemagglutination group 2 as well as types 20, 25, and 28. No virus-specific RNA could be detected in Ad-19 transformed rat or NIL-2 cells or in hamster tumors induced by Ad-19 cells. These data outline a fourth subgroup of human adenoviruses which share the ability to transform rat and hamster cells and which produce a common T antigen.
Genomic and transcriptomic profiling of Human Papilloma Virus (HPV)-positive head and neck squamous cell carcinomas (HNSCC) identifies a genetically distinct subgroup of head and neck cancers
Authors: K. L. Richards, S. Colella, K. A. Baggerly, S. Tsavachidis, L. C. Jas, D. E. Schuller, R. Krahe
Journal: Journal of Clinical Oncology (2005)

5507 Background: HPV is recognized as an important etiologic agent in a subset of HNSCC. HPV-positive cancers tend to be clinically distinct from HPV-negative ones in several ways, including a more favorable prognosis for patients with HPV-positive HNSCC. These different clinical characteristics imply an underlying biologic difference between the two tumor types. Methods: DNA and RNA samples from 24 HNSCC tumors and genetically matched normal tissues were analyzed. Oligonucleotide microarrays (Affymetrix, Santa Clara, CA) were used for genomic and transcriptomic profiling to determine global patterns of allelic imbalance (loss-of heterozygosity or amplification) and gene expression. Tumors were also examined for HPV status as well as genetic and epigenetic alterations in the CDKN2A/p16 and TP53/p53 tumor suppressor genes. HPV-positive (at both the DNA and RNA level) tumors were compared with HPV-negative tumors to identify HPV-related differences in patterns of gene expression and DNA alterations. Results: In total, 180 genes were found to show statistically significant differential expression between HPV-positive and HPV-negative tumors. These included immunomodulatory genes, and known tumor suppressor genes and oncogenes. Interestingly, HPV-negative tumors showed more genome-wide DNA alterations than HPV-positive tumors, most notably in a novel 3-Mb region in chromosome 9q where allelic imbalances occurred statistically significantly more often in HPV-negative tumors. Conclusions: HPV-positive tumors are genetically distinct from HPV-negative tumors, likely reflecting different mechanisms of oncogenesis. This has significant implications for the treatment and prevention of these different subgroups of HNSCC. No significant financial relationships to disclose.
Use of octreotide as second-line treatment for concurrent chemoradiation induced diarrhea refractory to loperamide
Authors: E. Topkan, U. Selek
Journal: Journal of Clinical Oncology (2004)

3704 Background: To prospectively evaluate efficacy of octreotide in treatment of chemoradiation induced diarrhea refractory to conventional loperamide treatment. Methods: Our study consists of 38 intractable diarrhea patients resistant to loperamide, out of 56 colon/rectum adenocarcinoma patients (T3–4NXM0) treated at Department of Radiation Oncology, Inonu University, between September 2002 and April 2003. All patients were treated with conventional radiotherapy (50.4 Gy, 1.8 Gy/fraction) with high-energy photons and concurrent 500mg/m2/week i.v. bolus 5FU. Thirty-eight patients had Grade 3 or 4 gastrointestinal toxicity during chemoradiation, according to National Cancer Institute Common Toxicity Criteria (NCI-CTC). Diarrhea failed to improve after 48 hours of p.o. loperamide (4 mg tid) administration on outpatient basis. As 38 patients were assigned to receive octreotide (150 mg tid) subcutaneously for 5 consecutive days, 8 patients who required parenteral support due to severe cramping, incontinence, gross bloody diarrhea were not included in the trial. Complete resolution of diarrhea was considered therapeutic response, whereas partial or no improvement in diarrhea to octreotide application for 5 days was documented as therapeutic failure. Results: Diarrhea, recorded as NCI-CTC Grade 3 & 4, was largely experienced in the first two weekly cycles of 5FU administration concurrent with radiotherapy; 19 (50%) patients in the 1st, 11 (31.6%) in the 2nd, 4 (10.5%) in the 3rd, and 3 (7.9%) in the 4th cycles. Octreotide application resolved diarrhea completely in 33 patients out of 38 cases (86.8%) without any side effects (1st day, 5; 2nd day, 10; 3rd day, 15; 4th day, 2; and 5th day, 1 cases). Five octreotide irresponsive patients (13.2%) discontinued chemoradiation to receive further supportive treatment by parenteral support of fluids and electrolytes with alternative antidiarrheal treatments. Conclusions: Daily subcutaneous octreotide application for five days seems to be an effective, tolerable second-line treatment for concurrent chemoradiation induced diarrhea refractory to loperamide. No significant financial relationships to disclose.
More on the use of bisphosphonates in the prevention and treatment of osteoporosis
Authors: Salvatore Minisola, Cristiana Cipriani, Alfredo Scillitani, Jessica Pepe
Journal: BMJ (2015)

Maraka and Kennel’s review of bisphosphonates in the prevention and treatment of osteoporosis omitted some information that could be important for doctors and patients.1

Alendronate is now available in a soluble form, which overcomes some of the gastrointestinal side effects associated with the ingestion of pills.

With …
Adjuvant chemotherapy of osteosarcoma: no runs, no hits, two men left on base.
Authors: J F Holland
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.1.4 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3543237 Adjuvant chemotherapy of osteosarcoma: no runs, no hits, two men left on base. J F HollandxJ F HollandSearch for articles by this author https://doi.org/10.1200/JCO.1987.5.1.4 First Page PDF © 1987 by American Society of Clinical Oncology