tbuckley/cabot-search huggingface dataset:
Scrambler therapy for the treatment of chronic post-mastectomy pain (cPMP) in breast cancer survivors.
Authors: Thomas J. Smith, Charles L. Loprinzi, Andrea L. Cheville
Journal: Journal of Clinical Oncology (2016)

253 Background: cPMP is chronic pain in the front thorax, axilla, and/or upper half of the arm beginning after mastectomy or lumpectomy persisting &gt; 3 months after treatment and presents with pain, allodynia and disability. cPMP occurs in half of all patients with breast cancer and is severe in 13% (Gartner R JAMA 2009). Epidural bupivacaine, memantine, gabapentin or venlafaxine may help prevent cPMP, but there are no established proven treatments. (Shen J, Up to Date 2016) Scrambler therapy (ST) is an FDA-cleared treatment for neuropathic pain supported by multiple trials in over 800 patients with cancer pain, chemotherapy induced neuropathic pain, back pain, and post herpetic neuropathy (PHN). (Majithia N JSSC 2016) Methods: We treated 2 women with cPMP with standard ST, with repeated treatment if the pain returned. ST was done with ECG pads above and below the pain for 45 minutes daily, until pain resolved, and repeated if/when pain recurred. Results: Case 1: A 60 year-old woman had bilateral mastectomy 2 years prior with cPMP like “a barbed wire bra”. Before treatment, her pain was 8, which decreased to 0-2 after 5 treatments. Her pain returned 4 months later and was successfully retreated. She resumed a more normal life and was able to taper and eventually stop her opioids. Case 2: A 56 year-old woman had deep aching cPMP for a year following chemo, Mastectomy, and RT. Her pain was 10, decreased to 0-1/10. Her pain returned 1 month later; 3 treatments reduced her pain from 4/10 to 0/10 and improved her quality of life, which lasted for several months until cancer recurrence. Conclusions: Scrambler therapy successfully treated cPMP in 2 patients with improved pain and quality of life, and enabled one patient to stop her opioids in line with new CDC guidelines. Scrambler therapy appears to hold promise, as it does in chemotherapy-induced neuropathy, failed back syndrome, PHN, low back pain and other conditions; prospective trials are indicated to further evaluate this treatment modality. [Table: see text]
Plasmapheresis therapy has no triglyceride-lowering effect in patients with hypertriglyceridemic pancreatitis
Authors: Kyohei Miyamoto, Masayasu Horibe, Masamitsu Sanui, Mitsuhito Sasaki, Daisuke Sugiyama, Seiya Kato, Takahiro Yamashita, Takashi Goto, Eisuke Iwasaki, Kunihiro Shirai, Kyoji Oe, Hirotaka Sawano, Takuya Oda, Hideto Yasuda, Yuki Ogura, Kaoru Hirose, Katsuya Kitamura, Nobutaka Chiba, Tetsu Ozaki, Taku Oshima, Tomonori Yamamoto, Keiji Nagata, Tetsuya Mine, Koji Saito, Motohiro Sekino, Tomoki Furuya, Naoyuki Matsuda, Mineji Hayakawa, Takanori Kanai, Toshihiko Mayumi
Journal: Intensive Care Medicine (2017)
Expression of programmed death ligand 1 (PD-L1) in malignant and nonmalignant pancreatic tissue.
Authors: Saqib Razzaque, Noman Ashraf, Julio C. Chavez, Mokenge Peter Malafa, Domenico Coppola, Gregory M. Springett, James Helm, Richard D. Kim
Journal: Journal of Clinical Oncology (2013)

215 Background: Programmed death 1 (PD-1) protein and its ligands (PD-L1 &amp; L2) play a key role in the evasion of the host immune system by tumor cells via inhibition of T-cells. It is of therapeutic interest that a number of tumor types selectively over-express PD-L1, since antibodies directed against PD-L1 have recently been shown to induce durable tumor regression. Methods: In this study we evaluated the expression of PD-L1 in pancreatic tissue obtained from 145 patients with localized pancreatic adenocarcinoma who underwent curative resection at our institution (stage IA – IIB). Of the 145 patients, 44 had paired pancreatic tissue samples of the tumor and adjacent non-malignant pancreatic tissue. These paired samples were used to compare expression of PD-L1 in malignant and nonmalignant tissue. Immunohistochemical staining was performed using rabbit primary antibody against PD-L1 (CD274/B7-H1) on formalin-fixed, paraffin-embedded core sections in tissue microarrays. Immunostain intensity and percentage cells stained were each scored on a scale of 0 to 3, with 3 being maximal. The product of intensity and percentage was used as a semi-quantitative measure of PD-L1 expression. Only patients with a product score greater than 0 on either the malignant or non-malignant tissue were included in this study. Results: PD-L1 expression (product score) was higher in 81% (36/44) of the malignant tissue samples than in paired non-malignant samples, equal in 7% (3/44) and lower in 11% (5/44). PD-L1 expression in malignant tissue (mean product score = 4.23) was significantly higher than the non-malignant pancreatic tissue (mean product score = 1.73) (p &lt; 0.0001). The median product score was also statistically significantly higher for malignant versus non-malignant (4 vs. 2) tissue. Conclusions: Pancreatic adenocarcinoma tumor cells express PD-L1 at a higher level than their non-malignant counterparts. Future trials should evaluate drugs targeting the PD-1/PD-L pathway in the treatment of pancreatic cancer.
Obesity, a risk factor for acute myeloid leukemia? Roswell Park Cancer Institute weighs in on the obesity debate.
Authors: H. J. Lee
Journal: Journal of Clinical Oncology (2010)

6559 Background: Obesity adversely affects outcome in pediatric acute lymphocytic leukemia and acute myeloid leukemia (AML). We asked if obesity affected outcome in 329 similarly treated adult AML patients. Methods: Patients were treated with high-dose cytarabine and idarubicin regimens at Roswell Park between 9/92 and 12/08. Cytarabine and idarubicin were based on actual weight. Results: There were 188 males and 141 females (median age: 57 years (yr), range 18-85). The median follow up was 12.9 (range, < 1-195) months. A total of 178 patients were < 60 yr and 151 patients were ≥ 60 yr. Karyotypes were favorable in 25 patients, intermediate in 144, unfavorable in 114 and of unknown risk in 46. White blood cell (WBC) count was < 100 x 109/L in 296 patients and ≥ 100 x 109/L in 33 at time of diagnosis. There were 229 patients (69.8%) with de novo AML and 100 (30.2%) with secondary AML. A total of 180 smokers; 101 never smoked and 48 with unknown smoking history. Patient distribution of body mass index (BMI) as defined by the World Health Organization (WHO): underweight (UW) 0.3%, normal weight (NL) 31.8%, overweight (OW) 36.4% and obese (OB) 31.5%. Patients' BMI ranged from 18.48 to 60.61. Overall survival (OS) by WHO classification for UW, NL, OW and OB was 1 vs. 28 vs. 35.5 vs. 27.3 months (p = 0.394). Progression-free survival (PFS) by WHO classification for NL, OW and OB were 26.5 vs. 31.5 vs. 33.9 months (p = 0.618). Age ≥ 60, unfavorable karyotype, secondary AML and positive smoking status had adverse impact on OS in multivariate analysis while BMI did not show a statistically significant difference between NL, OW and OB patients with a hazard ratio of 1 vs. 0.85 (95% confidence interval [CI]: 0.60-1.22) (p = 0.381) vs. 1.01 (95% CI: 0.71-1.48) (p = 0.887). Analysis of variance showed that age, karyotype, de novo presentation, and smoking but not BMI or WBC were statistically significant as independent predictors of OS and PFS. Interestingly, subgroup analysis of variance by different BMI categories showed a trend towards improved OS in OW patients compared to NL or OB in the young (18-39) but not in the > 40 yr population (p = 0.07). Conclusions: OW and OB patients performed as well as NL patients receiving high-dose cytarabine and idarubicin-containing regimens. No significant financial relationships to disclose.
Biomarker study in rectal cancer patients after 5FU-based radiochemotherapy: Evaluation of the prognostic capacity of thymidylate synthase in pretreatment biopsies and resected adenocarcinoma.
Authors: L. Conradi, A. Bleckmann, M. Schirmer, T. Sprenger, K. Homayounfar, H. A. Wolff, H. Becker, B. M. Ghadimi, T. Beissbarth, T. Liersch
Journal: Journal of Clinical Oncology (2011)

435 Background: Fluorouracil (5FU) remains the backbone of neoadjuvant radiochemotherapy (RCT) as well as adjuvant therapeutic strategies in multimodal treatment of rectal cancer patients. Due to its central role as the major target of 5FU thymidylate synthase (TS) is a promising biomarker in rectal cancer. We assessed TS in 208 patients with regard to its predictive/prognostic capacity for disease free DFS and overall cancer specific survival (CSS). Methods: 167 patients cUICC stages II (28%) and III (72%) received preoperative 5FU based RCT followed by total mesorectal excision (TME) A comparison group n = 41 received postoperative RCT after primary TME. All patients were treated after standardized protocols within phase-II/-III trials of the German Rectal Cancer Study Group. TS levels from pretreatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining for their impact on DFS and CSS. Additionally, a TS gene polymorphism (28 bp repeat) was analysed in respect to intracellular protein expression levels and prognostic significance. Results: Patients with low TS expression in pre-treatment biopsies showed a correlation with impaired CSS (p = 0.015). After neoadjuvant RCT there was evidence of lymph node metastases ypUICC stage III in 32.6%. Complete histopathologically confirmed tumor regression TRG 4 was achieved in 16 patients (9.5%). During follow-up (median 57 months) patients with low intratumoral TS expression and positive nodal status were at high risk for local and/or distant metastatic recurrence (p = 0.040). Analysis of the 28bp repeat revealed a correlation of *3/*3 genotype with high TS expression in pretherapeutical biopsies (p = 0.05). Conclusions: TS represents a prognostic biomarker in locally advanced rectal cancer indicating an unfavourable outcome for patients with low TS expression and might help to adapt adjuvant therapy regimens by stratifying patients according to their risk for cancer recurrence. No significant financial relationships to disclose.
Cyberpsychology advantages: A training on a mobile phone to control stress and anxiety in a day hospital oncology nurses’ sample.
Authors: C. Cognetta, R. Bollina, D. Toniolo, G. Riva, P. Belloni, C. Cozzi, F. Zannier, S. della Torre, P. Candido, G. Corradini, M. Bregni
Journal: Journal of Clinical Oncology (2011)

e16608 Background: In medical oncology, stress depend on severe proximity and deep emotive involvement with patients. Cyberpsychology’s approach could be significant for managing nurses’ stress and anxiety. This project aimed to test the effectiveness of mobile narratives usage applied to emotional changes and improving relaxing in a sample of oncology’s nurses. Methods: the experimental sample consisted of 30 female participants (N = 30), all oncology’s practical nurses, aged 33 to 53 (M = 43.,3; SD = 8.8). The sample, was randomized in two groups: Experimental group (EG) experienced 8 videos based on different natural surroundings with audio and video narratives, using UMTS mobile phones. A musical background goes with videos. Control group (CTRL) experienced 8 neutral videos, validated by Gross and Levenson, without audio narrative. Materials included 30 Nokia N70 used with headphones. Questionnaires were submitted at the start of the treatment (T1), before and after each multimedia audio– video session (from T2 to T9), at the end of this treatment (T10) and after 30 days later (T11). We used Job Content Questionnaire (JCQ), Mesure du Stress Psychologique (MSP), State – Trait Anxiety Inventory form Y (STAI), Coping Orientation to Problems Experienced (COPE), Emotion Regulation questionnaire (ERQ), International Test Commission –Sense of Presence Inventory (ITC –SOPI). Results: EG experienced a significant reduction in the anxiety level (P <0.05) at the end of the treatment. The second relevant result is related to an important reduction in stress’s level experienced only by the EG between the start of the treatment (T1 M = 5.4 ± 1.3), the end of the treatment (T10 M = 5.0 ± 1.5) and after 30 days later (T11 M = 5.0 ± 1.5). We found an enlarge of appraisal’s abilities (tested by ERQ) experienced only by the EG between the end of the treatment (T10 M =4.7 ± 0.9) and the follow – up (T11 M = 4.8 ± 0.8). Conclusions: This study shows the efficacy of mobile narratives in reducing the level of stress and anxiety experienced in oncology’s nurses. Are ongoing studies to apply Cyberpsychology to patients reducing anxiety about loosing hair in chemotherapy treatment.
Phase I trial of bortezomib in combination with paclitaxel in advanced solid tumor patients (pts)
Authors: C. L. Shapiro, B. Ramaswamy, D. Young, T. Lamb, D. Lucas, L. Shaaf, Z. Sahenk, M. Collamore, J. Byrd, J. Wright, M. Grever
Journal: Journal of Clinical Oncology (2005)

3104 Background: Bortezomib (B) (Velcade) inhibits the activation of NF-κB and may make tumor cells sensitive to chemotherapeutics, like paclitaxel, that activate NF-κB (Sunwoo et al Clin Ca Res 2001;7:1419–28). B and paclitaxel are additive in tumor growth delay models (Teicher et al Clin Can Res 1999;5:2638–45). We designed a phase I trial of escalating doses of weekly (wkly) B and paclitaxel. The primary objectives are to determine the dose of B that results in not more than 70–80% 20S-proteasome inhibition (20S-PI) when combined with paclitaxel, and to determine dose-limiting toxicity (DLT). Methods: Eligibility included ECOG performance status ≤ 2, and adequate end organ functions. Definitions of DLT: grade ≥ 3 non-hematologic and grade 4 hematologic toxicity (excluding asymptomatic neutropenia). Results: Twenty-five pts enrolled thus far. The first 4 pts were treated with wkly paclitaxel d1 and B d2 and 5 for 4 weeks (wks), cycles repeated every 6 wks. DLT and cumulative neurological toxicity led to the current schedule of wkly paclitaxel d1 and B d2 for 2 wks, cycles repeated every 3 wks. Dose escalations and results for 21 pts treated on the current schedule are described in the Table. Most adverse events (AE) were grade ≤ 2; most grade 3 AE were reversible lab abnormalities; and there were no grade 4 AE. 20S-PI 1 hr following B alone was 44% [range 24–72%], and 48% [range 6–74%] after B and paclitaxel. 20S-PI was not dose-dependent over the small range of B dose levels. At dose level 2, 2 pancreatic cancer pts had sustained significant decreases in CA 19–9 with 1 having SD and 1 having a PR (not confirmed). Conclusions: Thus far, the regimen has acceptable toxicity with evidence of antitumor activity. The trial will continue until the primary endpoints are reached. The results of p27 and Bax proteins in peripheral blood mononuclear cells, and serum inflammatory cytokines including TNF, IL-1, IL-6, C-reactive protein will be presented. Supported by NCI 2 UO1 CA- 076576–06. No significant financial relationships to disclose.
Role of αv integrins on perivascular mesenchymal cells in regulation of skeletal and cardiac muscle fibrosis
Authors: Iain Murray, Zaniah Gonzalez, James Baily, Jamie Smith, Alexandra Thomson, Stephen Greenhalgh, Ross Dobbie, Tim Kendall, Gillian Gray, David Griggs, Peter Ruminski, Hamish Simpson, John Iredale, Bruno Peault, Neil Henderson
Journal: The Lancet (2017)
Apricot-l: Results of a biomarker-based phase II randomized placebo-controlled study of apricoxib in combination with erlotinib in non-small cell lung cancer (NSCLC) patients.
Authors: B. J. Gitlitz, E. D. Bernstein, G. P. Keogh, E. S. Santos, G. A. Otterson, G. Milne, M. Syto, S. L. Zaknoen
Journal: Journal of Clinical Oncology (2011)

7528 Background: Apricoxib is a selective inhibitor of COX-2. The COX-2 pathway plays a key role in tumor growth, angiogenesis and resistance to therapy. In a phase I trial apricoxib and erlotinib were found to be safe and demonstrated a disease control rate of 60%. The recommended phase II dose was based on decreases in PGE-M; a urinary marker for tumoral COX-2 activity. Thus, this phase II trial used decreases in PGE-M to select pts for randomization. Methods: Pts with IIIB or IV NSCLC that had a 50% decrease from baseline PGE-M after a 5-day open-label run in of apricoxib were randomized. Pts were treated with erlotinib 150 mg PO daily and apricoxib/placebo 400mg PO daily. The primary objective was a 40% improvement in time to progression over the placebo arm. Results: 176 pts entered run-in and 120/176 (68%) were randomized in a 2:1 (active: placebo) fashion (82% of patients had at least a 50% drop). Gender: M/F: 67/53; age range 36-87 yrs.; 95% had an ECOG PS 0 or 1 and 5%, PS2. Most common adverse events (AEs) of any grade included; diarrhea (55%), rash (54%), fatigue (38%) and nausea (33%). More patients on the active combination arm discontinued due to AEs (7% vs 21%). In an analysis based on a pre-specified subgroup those pts in the ≤ 65 age group who were randomized to the active combination arm demonstrated statistically significant clinical benefit in all efficacy measures. Conclusions: This study is the first randomized placebo controlled trial to demonstrate a clinical benefit in a biomarker selected population of NSCLC pts using urinary PGE-M. Safety of this combination is acceptable, pts > 65 years on active drug experienced more study discontinuations due to AEs. Although overall ITT showed no benefit, DCR, TTP and OS were significantly improved with the active combination in pts aged 65 or younger. A phase III definitive trial is planned. ITT N=114 P value N=65 P value ≤ 65 HR DCR 46% vs 51% NS 35% vs 60% 0.018 Median TTP (months) 2.1 vs 1.8 0.97 1.4 vs 2.7 0.018 HR 0.5 (NA, 0.9) Median OS (months) 5.6 vs 5.9 0.83 3.8 vs 8.5 0.025 HR 0.4 (NA, 0.9)
Hematopoietic Progenitor Cell Transplantation from Parental Donors for Children with Sickle Cell Anemia and Stroke.
Authors: Paul Woodard, Gregory Hale, Wing Leung, Raymond Barfield, Kimberly Kasow, Renee Madden, Rupert Handgretinger, John Cunningham, Russell Ware
Journal: Blood (2007)
ER stress protein GRP78 as a therapeutic target combined with antiangiogenic therapy in renal cell carcinoma.
Authors: Kyung Seok Han, Na Li, Peter A. Raven, Estelle Li, Ladan Fazli, Martin E. Gleave, Alan I. So
Journal: Journal of Clinical Oncology (2013)

428 Background: Antiangiogenic therapy deprives oxygen and nutrition from the tumor. These stresses cause unfolded proteins in tumor cells. Glucose regulated protein 78 (GRP78) binds to unfolded proteins and its subsequent activation suppresses global mRNA translation to protect cells from excessive unfolded proteins. We investigated a potential role of GRP78 as a combined therapeutic target in renal cell carcinoma treated with antiangiogenic therapy. Methods: Renal cell carcinoma cells (Caki-1, Caki-2, UMRC-3, and UMRC-6) were used to investigate the effect of GRP78 knockdown, which was performed by small interfering RNA. Caki-1 xenografts were developed and treated with sunitinib 40mg/kg/day to evaluate in vivo expression of GRP78 during antiangiogenic therapy. Caki-1 cells stably overexpressing GRP78 were developed to investigate the role of GRP78 in cancer cell. Hypoxic stress was induced by 1% hypoxia chamber and hypoglycaemic stress was induced by glucose-free media. Downstream signalling pathways of GRP78 were evaluated by Western blots. Results: In vitro hypoxia and/or glucose deprivation induced GRP78 upregulation in Caki-1 cells. GRP78 was also induced in Caki-1 xenografts treated by sunitinib. Overexpression of GRP78 increased tumor proliferation in hypoxic and/or hypoglycemic stresses by activating PERK/eIF2α pathway and protected tumor cells from stress-induced apoptosis. Knockdown of GRP78 using small interference RNA inhibited cancer cell survival and induced apoptosis in renal cell carcinoma cells in vitro. GRP78 knockdown also sensitized renal cell carcinoma cells to ER stress-induced apoptosis and hypoxic and hypoplycemic stress-induces apoptosis. Conclusions: Antiangiogenic therapy induces ER stress by depriving oxygen and glucose from renal cell carcinoma. ER protein GRP78 has a critical role in protecting renal cell carcinoma cells from hypoxic and hypoglycemic stress induced by antiangiogenic therapy. Knockdown of GRP78 sensitizes RCC cells to apoptotic cell death from anti-angiogenic stresses. Our results suggest that GRP78 is a novel therapeutic target in renal cell carcinoma management.
Association of human papillomavirus with unique clinicopathologic features in patients with metastatic squamous cell carcinoma of the anal canal.
Authors: Van Karlyle Morris, Asif Rashid, Miguel A. Rodriguez-Bigas, Prajnan Das, Robert A. Wolff, George J. Chang, Christopher H. Crane, Jonathan Phillips, Aki Ohinata, Jane Rogers, Cathy Eng
Journal: Journal of Clinical Oncology (2014)

479 Background: The incidence of anal carcinoma in the United States continues to increase steadily, and infection with the human papillomavirus (HPV) is an established risk factor for the development of anal carcinoma. However, clinicopathologic characteristics of patients with metastatic squamous cell carcinoma of the anal canal according to HPV status have thus far not been defined. Methods: Records of patients treated for metastatic squamous cell carcinoma of the anal canal at the MD Anderson Cancer Center between June 2005 and August 2013 were reviewed. Patients were tested for the presence of HPV DNA by in-situ hybridization and/or the p16 oncoprotein by immunohistochemistry. Associations between the presence of HPV and clinicopathologic attributes were measured by calculation of odds ratios, and survival was estimated according to the Kaplan-Meier method. Results: Patients were followed for a mean of 50.2 months, and the mean age at diagnosis was 54.0 years. Among the 43 patient records reviewed, 39 tumors (90.1%) tested positive for the presence of HPV. Patients with HPV-negative tumors were more likely to have a strong (&gt; 30 pack-year) tobacco history (OR=18.5, p=0.018) and were more likely to develop brain metastases (OR=2.0, p=0.04). A faint association was observed between Caucasian ethnicity and HPV-positive tumors (OR=8.8, p=0.06). Median survival from the time of diagnosis of metastatic disease was 42.4 months, with a trend towards a worse survival seen among patients with HPV-negative tumors (HR for death 4.9, p=0.09). Conclusions: Differences in HPV status and prior tobacco exposure may identify two separate populations of patients with metastatic squamous cell anal carcinoma with different clinicopathologic phenotypes. Our results are similar to prior published data in patients with squamous cell carcinoma of the head and neck in which patients with HPV-positive tumors demonstrate improved survival outcomes. Data from additional patients will be presented.