tbuckley/cabot-search huggingface dataset:
Antitumorigenic effect of plumbagin by induction of SHP1 in human gastric carcinoma cell lines.
Authors: Jin Sung Koh, Jong-Jae Park, Moon Kyung Joo, Hyo Soon Yoo, Jiwon Kim, Yong Jeoung, Ho Kim, Jung Wan Choe, Beom Jae Lee, Jae Seon Kim, Young-Tae Bak
Journal: Journal of Clinical Oncology (2015)

74 Background: Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) is a plant-drived natural agent extracted from the root of Plumbago zeylanic. A recent study reported that plumbagin down-regulated the activity of Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway to show various anti-tumor effects. We aimed in this in vitrostudy to demonstrate the inhibition of JAK2-STAT3 pathway by plumbagin through inducing SH2-containing protein tyrosine phosphatase 1 (SHP1) expression in gastric cancer cell line. Methods: We performed Wetern blot to measure SHP1, phospho-JAK2/STAT3 level, and reverse transcriptase-polymerase chain reaction (RT-PCR) to evaluate target gene expression of STAT3. Several functional studies such as water soluble tetrazolium-1 (WST-1) assay, wound closure assay and matrigel invasion assay were also performed. Results: Plumbagin induced SHP1 expression and simultaneously down-regulated phospho-JAK2/STAT3 level via dose-and time-dependant manner in MKN28 cell, a gastric carcinoma cell line which has negative SHP1 expression. This effect was consistent when JAK2-STAT3 signaling was activated by interleukin-6, and ameliorated when cells were treated with prevanadate, a protein tyrosin phosphatase inhibitor. Furthermore, plumbagin significantly reduced gene expression of cyclin D1, VEGF1, survivin, MMP9, known target products of STAT3 activation in gastric cancinogenesis. The functional effect of plumbagin could be validated as inhibition of cell proliferation, migration and invasion, which are the results of activation of JAK2-STAT3 pathway in gastric cancer cells. Conclusions: Plumbagin is a potential negative regulator of cellular growth, migration and invasion by inhibiting both constitutive and inducible STAT3 activity through induction of SHP1 in gastric cancer cells.
In Utero Hematopoietic Cell Transplantation Using Haploidentical Parental Donors Reverses the Lethal Phenotype in Dogs with Canine Leukocyte Adhesion Deficiency.
Authors: William H. Peranteau, Yuchen Gu, Susan Volk, Laura M. Tuschong, Thomas R. Bauer, Andrea Badillo, Adam Kaye, Mark P. Johnson, Dennis D. Hickstein, Alan W. Flake
Journal: Blood (2006)
An interactive statistical imaging system and pilot application to characterize axillary lymph nodes in breast cancer
Authors: H. E. Kohrt, A. Kapelner, S. Holmes, P. P. Lee
Journal: Journal of Clinical Oncology (2008)

11059 Background: Clinical decisions in oncology are increasingly individualized and dependent upon accurate assessment of tumor biology, such as hormone receptor status. Imaging techniques are limited by subjective interpretation of staining patterns and limited tissue sampling leading to variability in patient care. We developed a novel imaging algorithm capable of quantifying multidimensional relationships between cell populations of interest on large tissue sections in a high-throughput fashion. Methods: An image analysis program was constructed in Java uniquely designed with supervised learning technology. Through an interactive visualization system, our technology allows a user to train the algorithm to detect cell types of interest. By incorporating statistical learning algorithms, cell classification can be improved rapidly with highly accurate results. The image analysis algorithm was applied to a series of IHC-stained sections of breast cancer-involved axillary lymph nodes. Four panels of three chromagens characterized the immune profile and breast tumor cells in 29,054 images. Cell type, location, and relative position to tumor were assessed by spatial analysis using R. Results: Following image training, cell classification remained highly accurate (>90%) among all images analyzed. Analysis quantified architectural patterns over an entire tissue section. Percent functional CD8 T cells with cytotoxic activity determined by granzyme B expression, percent CD4 T cells with T regulatory phenotype by CD25 and FoxP3 expression, and percent of dendritic cells actively presenting antigen were significantly dependent upon distance from lymph node-infiltrating tumor. Quantified cell populations of CD4 regulatory T cells and relative maturation status of antigen- presenting dendritic cells were statistically significant predictors of 5-year disease-free survival. Conclusions: We present imaging technology which is provided open-source for public use, that provides accurate quantification of cell populations in a high-throughput manner. We present novel, prognostically significant, architectural patterns of immune dysregulation dependent upon location of infiltrating breast cancer that warrant further study. No significant financial relationships to disclose.
Improved survival of patients with glioblastoma at NCI-designated clinical cancer centers.
Authors: Marlon G. Saria, Courtney Corle, Toni Rush, Santosh Kesari
Journal: Journal of Clinical Oncology (2013)

122 Background: Glioblastomas are considered the most life-threatening central nervous system (CNS) tumors. With such a rapidly progressing disease resulting in low survival rates, it is no surprise that many of the factors related to first-course treatment regimens are also related to patient survival. There is a need to investigate treatment patterns and survival trends so that optimal care standards can be developed for patients diagnosed with this devastating disease. Methods: Patients diagnosed with glioblastoma between 1999-2008 were identified in the California Cancer Registry. Survival estimates were calculated using Kaplan-Meier method and hazard ratios were calculated using Cox proportional hazards model. Multiple logistic regressions were used to determine the relationships between location of treatment and a patient’s first-course treatment regimen after adjusting for gender, age, race, socioeconomic status, type of insurance, and year of diagnosis. Results: 8,527 patients diagnosed with glioblastoma were included in the analysis. Patients receiving surgery, radiation, and chemotherapy as a first-course treatment regimen had a 1-year survival of 62.5% (95% CI: 61.6-63.4) compared to patients receiving any other treatment combination with a 1-year survival rate of 24.3% (95% CI: 23.7-24.9) (p&lt;0.0001). After adjusting for covariates, patients treated at National Cancer Institute-designated Clinical Cancer Centers (NCI-CCCs) were 1.31 (95% CI: 1.14-1.5) more likely to receive all three treatment options as a first-course regimen. Patients receiving care at NCI-CCCs had 11% increase in survival compared to patients receiving care elsewhere. Conclusions: Surgery, radiation, and chemotherapy given as a first-course treatment regimen for glioblastoma patients provide significant survival benefits and were more likely to be provided together at NCI-CCCs.
Phase II study of bevacizumab and cetuximab as neoadjuvant treatment in locally advanced rectal cancer: A preliminary security report.
Authors: G. Elvira, L. Torrecillas, G. Cervantes, A. A. Erzao Valle Solis
Journal: Journal of Clinical Oncology (2011)

627 Background: Concurrent chemoradiotherapy is the standard treatment in locally advanced rectal cancer. Bevacizumab and cetuximab are accepted today in the treatment of metastatic colorrectal cancer. We evaluate the activity and security of these drugs in the neoadyuvante setting. Methods: Ten patients have been included so far. Treatment consists in a first phase with induction treatment with capecitabine 2,000 mg/m 2 D1-14, oxaliplatin 130 mg/m 2 and bevacizumab 7.5 mg/kg every 3 weeks for two cycles. In sequential form a second phase that consist in external beam radiation therapy that was given at 50.4 Gy in 28 sesions concurrently with capecitabine 1,300 mg/m 2 /d continuous during radiotherapy with cetuximab 400 mg/m 2 every two weeks in patients with k-ras wild type. Results: 10 patients completed induction treatment and eight patients completed the concurrent phase. As of today, two patients are still on treatment. At this point, four patients have been operated; three patients are still waiting for surgery, and one avoided surgery. During induction treatment the main toxicity was disesthesias in eight patients, four patient presented grade 2 emesis, two presented grade 2 altered liver function test, two had grade 2 hand foot syndrome. One patient presented grade 3 hemorrhage. During the second phase, eight patients received cetuximab and presented rash grade 1-2, diarrhea grade 1 in five patients, emesis grade 1 in four patients, anemia grade 2 in two patients, proctitis grade 2 in four patients, and grade 3 in one patient. From four patients who were operated two presented complete pathological response and two have tumor persistence. Conclusions: The combination of chemoradiation with bevacizumab and cetuximab seems to be secure with no increment in toxicity and those presented are acceptable and manageable. No significant financial relationships to disclose.
First step of oral vinorelbine and capecitabine combination in advanced breast cancer patients: Feasability study
Authors: M. Gil-Delgado, M. Rocher, E. Boostandoost, D. Khayat
Journal: Journal of Clinical Oncology (2008)

1135 Background: The availability of chemotherapeutic drugs given by oral route represents a step forward in the management of cancer patients (pts). Vinorelbine and capectabine have established efficacy in metastatic breast cancer (MBC) with distinct mechanism of action. Oral vinorelbine (OVRL) interacts with tubulin and capecitabine (XLD) acts through antimetabolite properties of 5 FU. OVRL is rapidly absorbed (1.5–3h) with elimination half-life around of 40h. No pharmacokinetic interaction was found between these 2 compounds and its metabolites. Methods: The treatment schedule was initial dose of 60 mg/m2 of OVRL on day 1 and 8; XLD 1000 mg/m2 bid/daily from day 1 to 14 every 3 weeks. Cycles were repeated if ≥1,000/mm3 neutrophils and ≥100,000 platelets and not other G3–4 toxicities. XLD was adjusted from 1,000 mg/m2 to 900 mg/m2 or 750 mg/m2 in case of hand-foot syndrome or severe diarrhoea. Results: Between June 2003 and May 2007, 25 metastatic breast cancer pts were included in this trial. Median age: 68 years-old [range 42 - 87]. PS: 0–2. 8 pts received the combination as 1st-line, 5 pts as 2nd-line, and 12 pts ≥ 3rd-line. A median of 11 cycles [1 - 48] were given. One patient had G4 febrile neutropenia. One pt suffered from G3 diarrhoea, G2 mild diarrhoea was reported in 1/3 of pts after ORVRL lasting 12 hours. G2 hand foot-syndrome was observed in 4 pts (16%). Out of 23 evaluable pts, 21 had clinical benefits: 2 CR, 4 PR and 15 SD (90% tumour control). Conclusions: Oral vinorelbine and capecitabine combination is well tolerated and active in MBC pts allowing long-term treatment in ambulatory setting avoiding central venous line and infusions. In our experience, this combination seems to be correctly tolerated in elder patients (≥ 75 yrs-old). This combination should be tried in early stages for the next step planned in our institution that is ongoing, and in combination with new target therapies: monoclonal antibodies as trastuzumab for HER2 positive pts, and bevacizumab for HER-2 negative pts. No significant financial relationships to disclose.
Brief Report: The Euro‐Lupus Low‐Dose Intravenous Cyclophosphamide Regimen Does Not Impact the Ovarian Reserve, as Measured by Serum Levels of Anti–Müllerian Hormone
Authors: Farah Tamirou, Séverine Nieuwland Husson, Damien Gruson, Frédéric Debiève, Bernard R. Lauwerys, Frédéric A. Houssiau
Journal: Arthritis & Rheumatology (2017)

The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Müllerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC.Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected.Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43).The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant.
Propensity score matched analysis of metastasis-free survival for patients with high-risk prostate cancer treated with definitive radiation therapy or radical prostatectomy.
Authors: Marshall Meeks, Stephanie Subasic Markovina, Joel Vetter, Alethea Paradis, Jeff M. Michalski, Gurdarshan Singh Sandhu
Journal: Journal of Clinical Oncology (2015)

47 Background: National Comprehensive Cancer Network (NCCN) category 1 recommendation for localized high risk prostate cancer (HR-PCa) is definitive radiation therapy (RT) and androgen deprivation therapy (ADT). Radical prostatectomy (RP) is also an accepted treatment for patients with localized HR-PCa. Here we report a propensity score-matched analysis of institutional outcomes for patients with HR-PCa treated with RP or RT. Methods: Medical recor ds of patients with localized NCCN HR-PCa treated at our institution from 2002-2011 were reviewed. RT consisted of 73.8-77.4 Gray to the prostate and seminal vesicles; regional lymph nodes were treated for pre-treatment probability of involvement ≥15%. A combination of nearest neighbor propensity score matching on age, Adult Comorbidity Evaluation-27 score [a validated comorbidity index], prostate specific antigen (PSA), biopsy Gleason, and clinical T-stage (cT) and exact matching on PSA, biopsy Gleason, and cT was performed. Multivariate cox-proportional hazards regression was used to compare metastasis-free survival (MFS) and overall survival (OS) (calculated from date of diagnosis). Results: 246 patients were identified (160 RP and 86 RT). Propensity score matching resulted in 62 matched pairs. For the RP group, minimally invasive surgery (70.9%) and lymph node dissection (100%) were common. ADT was administered to 37.1% and 80.6% of patients receiving RP and RT, respectively. Median follow-up was longer for the RT group (51.4 vs 41 months, p = 0.004). Five-year rates of metastasis for RT and RP were 8.9% and 33% (p = 0.003), and for death were 25.9% and 17.6%, respectively (p = 0.31). MFS was significantly better for patients treated with definitive RT compared to RP, while OS was not different (Table). Conclusions: In our cohort with HR-PCa, treatment with RT resulted in a MFS advantage over RP. This was not accompanied by an improvement in OS.The difference in MFS may possibly be related to the importance of early adjuvant ADT. [Table: see text]
Efficacy of perioperative immunonutritional support with immune-modulating nutrients for postoperative infection-related complications, such as surgical site infection, in elective gastrointestinal cancer surgery.
Authors: Y. Shibata
Journal: Journal of Clinical Oncology (2011)

e19716 Background: Prolonged hospitalization is associated with an increased risk of surgical site infection (SSI) developing as an infectious complication after digestive tract surgery. Such complications are troublesome to the patient as well as the surgeon. Inflammation is an essential component of SSI after major intestinal surgery. The aim of this study was to assess the effect of immune-modulating nutrition on clinical outcomes in patients undergoing elective surgery for gastric and colorectal cancer. Methods: In this prospective, randomized, single-center clinical trial, 330 patients received nutritional supplementation with the ArginaidTM formula (arginine enhanced diet, ISOCALR) before and after elective gastrointestinal cancer surgery between July 2005 and June 2007. One group (Arg-group, 142) received 3 packs of ArginaidTM/day for 2 days before surgery and on postoperative days 4 to 9. The other group (Cont-group, 188) did not receive Arginaid. Clinical variables, postoperative complications, and the length of the hospital stay were recorded. Results: Preoperative characteristics (age, sex, ASA, nutritional status) were similar in the two groups. The rate of postoperative infections and complications did not differ significantly between the Cont-group (23.4%) and Arg-group (22.5%). However, the length of the hospital stay was significantly longer in the Cont-group (17 days) than in the Arg-group (14 days; p<0.0001). On multivariate analysis, a longer hospital stay was associated with lack of nutritional supplementation, advanced age (70 years or older), operation time (5 hours or longer), and wound class and infection. Conclusions: Our results indicate that arginine-rich immunonutritional support suppresses SSI and promotes recovery after surgery in patients with gastric and colorectal cancer. Immune-modulating nutritional treatment effectively decreases and controls surgery-related complications.
Rapid isolation of imageable circulating tumor cells.
Authors: R. M. Hoffman, K. Kolostova, D. Pinterova, V. Bobek
Journal: Journal of Clinical Oncology (2011)

e21011 Background: Circulating tumor cells (CTC) are potential precursors of metastasis. They are also of use in diagnosing malignancy and for prognostic purposes. Our laboratory has previously isolated CTC from orthotopic nude mouse models of human prostate cancer cells where the PC-3 cancer cells express green fluorescent protein (GFP). It was found that only orthotopic tumors produced CTC and not subcutaneous tumors, which may explain why orthotopic tumors metastasize and subcutaneous tumors do not. However, in this previous study, CTC were observed only after culture. Methods: The present study used the GFP-expressing PC-3 orthotopic model and immunomagnetic beads coated with anti-EpCAM and anti-PSMA. Results: GFP-expressing CTC were isolated within 15 minutes and were readily visualized by GFP fluorescence. The immunomagnetic-bead-captured GFP-expressing PC-3 CTC could be immediately placed in 3-dimensional sponge cell culture where they proliferated. Conclusions: The combination of GFP-expression and immunomagnetic beads is very powerful method to obtain CTC for either immediate analysis or for biological characterization in vivo or 3-dimensional culture for further use in the drug sensitivity testing.
Development of a capital investment strategy for radiation (RT) equipment in Ontario.
Authors: Eric Gutierrez, Padraig Richard Warde, Dianne Belfour-Barnett, Garth Matheson, Elaine Meertens, Lisa Favell
Journal: Journal of Clinical Oncology (2013)

279 Background: To ensure appropriate access to radiation treatment (RT) for Ontario cancer patients for the next decade and that future capital investments in radiation equipment are appropriately timed and strategically placed, Cancer Care Ontario (CCO) has updated its RT Capital Investment Strategy. The strategy was designed around 4 core principles: i) recognizing treatment machine capacity should match the demand resulting from increasing cancer incidence rates and increasing utilization rates as per CCO goals; ii) keeping pace with advancing technology; iii) ensuring value for money by maximising the use of current infrastructure; and iv) minimizing costs through centralized planning and procurement processes. Methods: A multidisciplinary provincial expert panel reviewed and revised the planning parameters used to project treatment demand and required capacity (including fractions of RT per treated case, number of cases treated per hour, uptime of treatment units). The panel reviewed current practice, impact of new and emerging treatment technologies and benchmarks from other jurisdictions. To project the future demand for radiation therapy, growth in cancer incidence (by county) as well as modest improvement in RT utilization rates were assumed. Results: Recommendations included: i) moving to 12-hour treatment days in all large centres and on 50% of equipment in centres operating fewer than 6 treatment units; ii) ensuring appropriate funding for the replacement of existing RT equipment; iii) equipping constructed rooms in 4 regional cancer centers – thereby adding 6 linacs; iv) equipping swing bunkers across the province – thereby adding 10 linacs; and v) planning for the construction of new facilities to add RT capacity in 3 regions of the province. Conclusions: Funding to implement recommendations from previous capital investment strategies has resulted in an equitable distribution of RT resources across the province. We believe the planning strategies and recommendations outlined in the strategy will improve access to quality RT care as close to home as feasible for Ontario patients.
Addressing psychiatric needs in an adult comprehensive cancer center.
Authors: Jody A. Underwood, Elaine McDonald, Kathleen Higginbotham, Susan F. Korber
Journal: Journal of Clinical Oncology (2015)

218 Background: The Rhode Island Hospital Comprehensive Cancer Center (RIH-CCC) sought to develop collaboration between psychiatry and social work to ensure comprehensive mental health care for the Centers’ adult patients. New patients are screened for distress using the NCCN Screening Tool for Measuring Distress. The NCCN Distress Thermometer measures patient’s distress using a 0-10 scale and documents the contributing psychosocial factors. The Cancer Center, in collaboration with psychiatry, developed standards for follow-up care. Those patients who indicate their distress as 4-7 are contacted by social work within 3 business days. The patients who identify their distress as 8-10 have social work follow up within 1 business day. Methods: The RIH-CCC mental health team consists of 4 full time clinical social workers and 2 psychiatrists. The social workers receive the patient’s distress scale after which they complete a comprehensive psychosocial assessment and develop a plan of care based on the urgency and complexity of the required interventions. The patients who require psychiatric evaluation are scheduled by the social work team to meet with the RIH-CCC psychiatrist for further assessment and evaluation. Results: Data was analyzed for the quarter of November 2014 to January 2015. The Center evaluated 1033 new patients. Of those, 119 completed a distress thermometer indicating a level of distress greater than 4 (average score of 6.6). Of the 119 patients seen by social work, 88 (74%) were in need of follow up care which often included further assessment by the on-site psychiatrists. Conclusions: Depression is estimated to occur in approximately 25-30% of adult cancer patients. Untreated and undiagnosed distress can have an adverse effect on cancer treatment. Our Centers’ results indicate that a significant number of those patients who identified as distressed were in need of further psychiatric evaluation and treatment. The strong collaborative relationship between on-site psychiatry and clinical social work promote early access and intervention to this challenged population.