tbuckley/cabot-search huggingface dataset:
Phase II study of bevacizumab (B), camptosar (I), high-dose 24-hour continuous intravenous infusion of floxuridine (F) and leucovorin (L) in patients with previously untreated metastatic colon cancer. (B-IFL)
Authors: B. Ardalan, M. Feagans, D. Mezentsev, C. Jones, P. R. Subbarayan, G. Walker, M. Sapp, K. Stephenson, J. Ness, D. Franceschi, A. Livingstone
Journal: Journal of Clinical Oncology (2009)

e15114 Background: In a previous study, IFL was used in patients (pt) with untreated metastatic colon cancer and a median overall survival (MOS) of 31 months (m). In the current study we added B to IFL to determine toxicity profiles (TP) and the response rate (RR) to the B-IFL regimen. The primary end-point is MOS Methods: Each cycle involved 6 weeks (wks) of treatment. The treatment cycle consisted of a 90 minute infusion of I (110 mg/m 2 ), followed by a 24 hour infusion of F (120mg/kg) and L (500 mg/m 2 ) on wks 1, 2, 4, 5. Pt received B (7.5mg/kg) over 90 minutes on wks 1 and 4 prior to IFL. No therapy was given on wks 3 and 6. Eligible pt received 2 cycles of B-IFL followed by CT scan. Quality of life data and thymidylate synthase expression in peripheral blood mononuclear cells was monitored Results: 22 pt with a median age of 57 (38–82), 11 males and 11 females were enrolled. Median KPS was 90% (50–100). 8 pt (36%) had bilobar liver disease and involvement of 1 other organ, 6 pt (27%) had bilobar liver disease with involvement of ≥ 2 other organs; 5 pt (23.5%) had bilobar liver disease; 2 pt (9%) had abdominal carcinomatosis; 1 pt (4.5 %) had involvement in one liver lobe. Grade (Gr) 4 toxicity: pulmonary embolus 1 pt (5%) incidental CT finding. Gr 3 occurred in 11 pt (50%); DVT, diarrhea (Drh) 3 pt (14%); fatigue (Ftg), infection, port site thrombosis (Pst), small bowel obstruction 2 pt (9%); wound dehiscence 1pt (5%); Gr 2 and 1: constipation; Drh; Ftg; nausea; neutropenia; Pst; alopecia; anorexia; mucositis. 17 pt remain alive with median follow up of 15 m (2–28). 5 pt have died due to progression of disease. The estimated median time to progression was 13 m with corresponding lower 95% confidence bound of 8.4 m. Kaplan-Meier estimate at 2 yr survival is 61% (95% CI 27–83%). RR in 21 pt was 67% (95% CI: 43–85%). Conclusions: B-IFL regimen has a manageable TP. RR and progression free interval were promising. Pt accrual is ongoing. Supported by Pfizer. No significant financial relationships to disclose.
Cancer Cell Dissemination and Homing to the Bone Marrow in a Zebrafish Model
Authors: Antonio Sacco, Aldo M. Roccaro, Dongdong Ma, Jiantao Shi, Yuji Mishima, Michele Moschetta, Marco Chiarini, Nikhil Munshi, Robert I. Handin, Irene M. Ghobrial
Journal: Cancer Research (2016)

Advancement of many solid tumors and hematologic malignancies is frequently characterized by dissemination and homing of cancer cells to the bone marrow (BM). Methods to quantitatively characterize these key steps of the metastatic cascade in mammalian models are currently limited and do not offer opportunities to perform rapid, large-scale genomic, or drug screening. Because of their optical clarity, we used zebrafish to develop an in vivo model of cancer cell dissemination and homing to the BM. We performed intracardiac injection of multiple myeloma (MM) cells derived from human BM or cell lines and monitored their migration to the caudal hematopoietic tissue (CHT), the region where hematopoiesis occurs in the zebrafish embryo, which recapitulates a BM-like niche. Transcriptomic analyses confirmed that MM cells homing to the CHT displayed gene-expression differences compared with MM cells outside of the CHT, including significant enrichment for genes known to regulate interleukin-6 (IL6) signaling, cell adhesion, and angiogenesis. Collectively, our findings point to the zebrafish as a valuable model in which to study cancer cell homing to the hematopoietic niche and to establish a screening platform for the identification of factors and mechanisms contributing to the early steps of bone metastasis.
Melanoma Risk and Citrus Consumption
Authors: Steven Lehrer, Sheryl Green, Kenneth E. Rosenzweig
Journal: Journal of Clinical Oncology (2016)

TO THE EDITOR: Wu et al report that citrus consumption increases risk of cutaneous malignant melanoma. The authors state that citrus fruits contain psoralens and furocoumarins, which sensitize the skin to UV radiation and are potent carcinogens. Consumption of citrus fruits and juices more than 1.6 times per day (95% CI, 1.14 to 1.63) resulted in a risk for developing melanoma of 1.36. The results of Wu et al contradict the results of Fortes et al, who found that citrus fruit consumption protects against melanoma. Low consumption (up to two times per week) had no protective effect (odds ratio [OR]5 1). Medium citrus consumption (three to four times per week) had an OR of 0.79 (95% CI, 0.47 to 1.32, adjusted for sex, age, education, hair color, skin phototypes, number of nevi, presence of freckles in childhood, and sunburns in childhood). High citrus consumption (four to five times per week) had an OR of 0.51 (95% CI, 0.32 to 0.80; P 5 .003; Wald test for trend). Citrus consumption is widely advocated because it reduces the risk of coronary heart disease, cancer, and other forms of illness. Therefore, further study would be worthwhile.
Evaluation of 5-FU metabolism-relating enzyme gene expression levels using quantitative real-time RT-PCR from formalin fixed parafine embedded samples
Authors: M. Terashima, Y. Odashima, S. Ohtani, N. Soeta, F. Ohsuka, S. Kashimura, Y. Hoshino, M. Kogure, M. Gotoh, K. D. Danenberg, P. V. Danenberg
Journal: Journal of Clinical Oncology (2006)

13034 Background: We have previously reported that tumors with high orotate phosphoribosil transferase (OPRT) and low dihydropyrimidine dehydrogenase (DPD) mRNA expression levels showed remarkable sensitivity to 5-fluorouracil (5-FU) by real-time RT-PCR using fresh frozen (FF) tumor samples. However, the use of fresh frozen samples has some limitations. The use of formalin fixed parafine embedded (FFPE) samples has great advantage to apply these technologies for clinical settings. In order to investigate the feasibility of real-time RT-PCR from FFPE samples to predict sensitivitiy to 5-fluorouracil (5-FU), we investigated the gene expression levels of 5-FU metabolism-relating enzymes by real-time RT-PCR from FFPE samples and compared the results from FF samples in gastric and colorectal cancer. Methods: FFPE samples and FF samples were obtained from 46 patients with gastric cancer and 29 patients with colorectal cancer. Gene expression levels of tymidylate synthase (TS), OPRT, thymidine phosphorylase (TP) and DPD were determined by quantitative real-time RT-PCR. In FFPE samples tumor tissue was obtained using laser captured microdissection (LCM). Tumor sensitivity to 5-FU was evaluated by in vitro ATP assay. Results: Gene expression levels of TS, TP, DPD determined from FFPE samples significantly correlated with those from FF samples. Although respective gene expression levels alone failed to show signifcianct correlation with the in vitro 5-FU sensitivity, statistically significant correlation was noted either from the samples of FF or FFPE in both gastric (FF: r = 0.660, FFPE: r = 0.780) and colorectal cancer (FF: r = 0.780, FFPE: r = 0.660), when OPRT/DPD mRNA ratio was applied for comparison with the results of 5-FU sensitivity. Thus, high OPRT/DPD ratio determined from FFPE samples resulted in high sensitivity to 5-FU. Conclusions: From these results, it is suggested that sensitivity to 5-FU is predictable by quantitative RT-PCR using FFPE samples. Measurement of 5-FU metabolism-relating enzyme gene expression level from FFPE samples appeared to be feasible for predicting 5-FU sensitivity and to have great advantage to apply the molecular predicting assay in clinical settings. [Table: see text]
Glucose Tolerance and Glycosuria in the General Population
Authors: N H PIERCE
Journal: BMJ (1963)

ICE-COOLINGMEDBsRITISHNAL 655 17 hours the damage was sometimes partially reversible.However, with 24 hours' preservation severe irreversible damage resulted.The interpretation of the microscopical changes in relation to those occurring in renal homografts is discussed.
Characteristics and outcomes of cancer patients ≥80 years treated with chemotherapy at a comprehensive cancer center
Authors: P. Jiang, M. Choi, D. Smith, L. Heilbrun, S. M. Gadgeel
Journal: Journal of Clinical Oncology (2006)

8548 Background: The percentage of cancer patients ≥ 80 years old is expected to rise in the United States. However data are limited on use of chemotherapy in this group of patients. Methods: Retrospective identification of patients who received systemic chemotherapy at our cancer center between 1/1/2000 to 12/31/2004 was performed using the computer generated pharmacy data and medical records. Patients who had diagnosis of cancer and ≥ 80 years were included in the study; patients receiving only supportive care, hormonal therapy, or oral chemotherapy were excluded. The protocol for this study was approved by the Wayne State University IRB. Results: A total of 133 patients ≥ 80 years who received chemotherapy was analyzed. The median age was 83 and 31% of the patients were ≥ 85 years. There were more females (61%) than males (39%). The gender distribution was more even (47% v. 53%) after excluding gender specific tumors. The racial distribution was diverse- Whites 65 (49%); Blacks 41 (31%); Other 18 (13%); Unknown 9 (7%). 16% of the patients had hematologic malignancy and 84% had solid tumors. Gynecological cancers (32%) followed by aerodigestive cancers (26%) were the most common solid tumors. Solid tumor patients primarily had regional (48%) or distant (45%) disease. During the first regimen, 512 cycles of chemotherapy was delivered with a median of 3 cycles per patient (range 1–24 cycles); 40% of patients received only 2 cycles of chemotherapy. 64% of patients were able to receive chemotherapy without 2nd cycle delay. The distribution of single or multidrug regimens was fairly similar; Solid tumors 52% v. 48%; Hematologic cancers 43% v. 57%. Carboplatin and paclitaxel (22%) was the most common regimen among solid tumor patients. 26% of all patients received a second regimen. The 1 year survival rates among hematologic cancer and solid tumor patients were 65% and 48%, respectively. Stage of disease was the only statistically significant factor predicting survival. Conclusions: In this diverse group of cancer patients ≥ 80 years old and selected for chemotherapy, the treatment was feasible. The survival outcomes in this elderly population were comparable to those of a younger patient population suggesting that the treatment is beneficial. No significant financial relationships to disclose.
Primary tumor tissue levels of TIMP-1 and outcome following chemotherapy with docetaxel monotherapy or docetaxel in combination with gemcitabine in patients with locally advanced or metastatic breast cancer.
Authors: C. L. J∅rgensen, E. Balslev, K. D. Bjerre, A. Bartels, S. M∅ller, B. Ejlertsen, N. Brünner, D. L. Nielsen
Journal: Journal of Clinical Oncology (2010)

1079 Background: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is recognized to protect against apoptosis, and previous studies have demonstrated that high levels of TIMP-1 in primary tumor tissue are associated with poor response to anthracycline-containing chemotherapy in adjuvant as well as metastatic treatment of breast cancer (Schrohl et al., Clin. Cancer Res. 2006; Klintman et al. Breast Cancer Res. Treat. 2009; Schrohl et al., BMC Cancer 2009; Willemoe et al., EJC 2009). The purpose of the present study was to evaluate whether TIMP-1 immunoreactivity also predicts sensitivity/resistance to taxanes. Methods: Tissue micro arrays from the primary tumor tissue from 260 patients with locally advanced or metastatic breast cancer randomly assigned to docetaxel or docetaxel plus gemcitabine were included. Assessment of TIMP- 1 status was performed using immunohistochemistry and tumor samples were regarded as positive if epithelial breast cancer cells were stained by the anti-TIMP-1 monoclonal antibody VT7 (S∅rensen et al., J. Hist. Cytochem. 2006). Relationships between the effects of chemotherapy and TIMP-1 status were analyzed using univariate analysis. Endpoints were best clinical response (BCR, not confirmed) and progression-free survival (PFS). Results: Since there were no differences in BCR or PFS between the two randomization arms, the patient cohort was pooled. 150 (58%) of the tumors were classified as tumor cell TIMP-1 positive. Among TIMP-1 positive patients 46 (31%) obtained complete response (CR) or partial response (PR), while 39 (35%) of the TIMP-1 negative patients had CR or PR (Fisher's exact test, p= 0.43). Applying PFS as end-point no significant difference between TIMP-1 negative versus TIMP-1 positive patients was observed (log-rank test, p= 0.29). Conclusions: The present study is the first to demonstrate that TIMP-1, a marker of anthracycline resistance, is not associated with a poor response to docetaxel in patients with locally advanced or metastatic breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Patent application on TIMP-1 as a predictive biomarker
Breast cancer diagnosis and treatment in a safety net setting: Differences between insured and uninsured patients
Authors: N. J. Farrell, C. J. Bradley, L. M. Schickle
Journal: Journal of Clinical Oncology (2007)

6566 Background: Despite the safety net system and many other means of providing free or low cost care to women with breast cancer, disparities in health outcomes between uninsured and insured women with breast cancer exist. In this study, we evaluate the role of health insurance on breast cancer treatments at a large safety net hospital system. Methods: From the patient population at the Massey Cancer Center at Virginia Commonwealth University Health Care System (a large regional safety net provider), we selected women ages 21 to 64 diagnosed with breast cancer between January 1999 and March 2006 (n=1,381). We used billing records to identify health insurance status of these patients. First, we compared the stage of disease and tumor size at diagnosis for women with and without insurance. Next, we compared the number of days between diagnosis and surgery and the number of days between surgery and chemotherapy initiation. Finally, we estimated the number of days it took these groups of women to complete a common adjuvant chemotherapy regimen of doxorubicin plus cyclophosphamide (AC) or doxorubicin plus cyclophosphamide followed by paclitaxel (ACT). Results: Our analysis shows that women without insurance were more likely to have more advanced cancers and correspondingly larger tumors. Uninsured women experienced considerable delays from the date of diagnosis to surgery and from surgery to chemotherapy initiation compared with insured women (21.5 and 22 days longer, respectively). Uninsured women also took significantly longer to complete adjuvant chemotherapy regimens relative to insured women (4 and 26 days for AC and ACT, respectively). Conclusions: To understand the disparities that exist in breast cancer outcomes among women with and without health insurance, we must understand the different experiences these groups of women have with treatment. In this study, uninsured women had more advanced cancers, and experienced considerable delays receiving and completing treatment relative to insured women. Our study demonstrates the value of health insurance in the timely provision of health care even in a safety net setting where care is guaranteed. No significant financial relationships to disclose.
Aberrant DNA Methylation Is Associated With Poor Outcomes In Juvenile Myelomonocytic Leukemia
Authors: Hirotoshi Sakaguchi, Hideki Muramatsu, Xinan Wang, Yinyan Xu, Yoko Hibi, Nozomu Kawashima, Atsushi Narita, Sayoko Doisaki, Nao Yoshida, Asahito Hama, Yoshiyuki Takahashi, Hideki Makishima, Kiyofumi Yamada, Jaroslaw P. Maciejewski, Seiji Kojima
Journal: Blood (2013)
Dental care and tooth extraction as a risk factor for developing osteonecrosis of the jaw after long-term bisphosphonate therapy in patients with metastatic breast cancer
Authors: P. Spadaro, V. Pitini, G. Altavilla, M. Ingemi, G. Dottore
Journal: Journal of Clinical Oncology (2007)

1076 Background: Association between osteonecrosis of the jaw (ONJ) and bisphosphonate treatment in patients (pts.)with Multiple Myeloma, breast cancer and prostate cancer has been increasingly reported in the literature. Risk factor for this complication include presence of infection, recent dental extraction and any oral surgical procedure with bone exposure. Methods: This is a retrospective review of our experience with patients diagnosed with bone metastasis secondary to breast cancer, who developed ONJ while treated with bisphosphonates, between January 2002 and December 2006. Presentation, age, dental status, and outcome were reviewed. Logistic Regression was used to test for statistical significance. Results: 100 pts. with bone metastasis secondary to breast cancer, median age 63 years, treated with bisphosphonates were reviewed. ONJ developed in 5 (5%) pts. Age did not impact occurrence of ONJ. All 5 patients developed ONJ after a minimum of 100mg of Zoledronic Acid and 2700mg of Pamidronate. All pts. had a history of previous tooth extraction and inadequate dental care. Three pts. were treated with debridement and antibiotics and their lesions healed. Two pts. ended up suffering from a chronically exposed bone. Conclusions: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our patients. Our data suggests a strong association between dental care, tooth extraction, and the development of ONJ. No significant financial relationships to disclose.
Functional analysis of a novel lipogenic factor, FARM (fatty acid-related molecule), over-expressed in prostate cancer cells
Authors: Hidewaki Nakagawa, Kenji Tamura, Toshihide Kobayashi, Mutsuo Furihata, Su-youn Chung, Motohide Uemura, Shingo Ashida, Tsuenharu Miki, Tomoaki Fujioka, Taro Shuin, Yusuke Nakamura
Journal: Cancer Research (2008)

2730   A number of epidemiological and laboratory studies have implicated that lipid metabolism is likely to play important roles in prostate carcinogenesis and prostate cancer (PC) progression, but how lipids are involved with PC at molecular level is largely puzzled. Through genome-wide cDNA microarray analysis coupled with microdissection of PC cells, we identified a novel lipogenic gene, FARM (fatty acid-related molecule), as a trans-activated gene in PC cells. RT-PCR and northern blot analysis confirmed its overexpression in PC cells, but its expression was also observed at a low level in normal prostate restrictively among adult normal organs examined. Immunohistochemical analysis using anti-FARM antibody further confirmed the elevated expression of FARM in PC cells comparing to normal prostate epithelial cells and PC precursor lesion PINs. FARM expression was regulated by androgen receptor-SREBP (sterol regulatory element-binding protein) pathway as well as many other lipogenic factors. Functionally, knockdown of FARM by siRNA in PC cell line resulted in drastic attenuation of PC cell growth, suggesting that FARM expression could be essential to PC growth or viability. It is notable that knockdown of FARM by siRNA reduced neutral lipids, saturated long-chain fatty acid, and intracellular androgen content in PC cells. Concordantly, high-fat diet in xenograft mouse model promoted FARM-expressing PC cell growth, but not FARM-negative cell growth, accompanied with increasing intracellular content of saturated long-chain fatty acid and androgen in PC cells. Our findings on this novel lipogenic factor can shed light on the mechanism of prostate carcinogenesis associated with fat diet and lipid metabolism.
Neuroblastoma and treatment-related myelodysplasia/leukemia: the Memorial Sloan-Kettering experience and a literature review.
Authors: B H Kushner, N K Cheung, K Kramer, G Heller, S C Jhanwar
Journal: Journal of Clinical Oncology (1998)

PURPOSE To assess treatment-related myelodysplasia/leukemia (t-AML) in neuroblastoma patients by a review of the Memorial Sloan-Kettering Cancer Center (MSKCC) data and the literature. PATIENTS AND METHODS We studied 380 previously untreated and treated MSKCC patients. Low-risk patients received no cytotoxic therapy. High-risk patients received the N4, N5, or N6 regimens. Dosing per cycle and cumulative dosing of leukemogenic agents peaked with N6, which included four cycles of cyclophosphamide 4,200 mg/m2 and doxorubicin 75 mg/m2, plus three cycles of cisplatin 200 mg/m2 and etoposide 600 mg/m2. We reviewed the literature. RESULTS t-AML occurred in six MSKCC patients, which included three of 53 patients in whom the only chemotherapy consisted of N6, and three patients treated for relapsed or refractory neuroblastoma; no case of leukemia emerged among the 50 low-risk patients. Four cases were found incidentally in routine follow-up bone marrow tests. The 36-month cumulative incidence of t-AML in the N6 cohort was 7% (95% confidence interval, 0 to 15). Published data parallel the MSKCC experience in that t-AML after neuroblastoma was once rare but has become less so since the mid-1980s, when the intensified use of topoisomerase-II inhibitors and alkylators first gained wide acceptance and produced better response rates and longer survival. CONCLUSION Neuroblastoma itself is not associated with a host susceptibility to leukemia. However, current neuroblastoma treatment programs that use high-dose cyclophosphamide, cisplatin, and topoisomerase-II inhibitors may entail a considerable risk for t-AML. The incidence of t-AML in neuroblastoma patients may be underestimated because treatment and clinical factors can mask its presence. Efforts to devise effective but less leukemogenic treatment for neuroblastoma or to truncate leukemogenic therapy, eg, by exploiting molecular techniques for the early identification of complete remission, are warranted.