tbuckley/cabot-search huggingface dataset:
Incidence of engraftment fever post autologous transplant for lymphomas and analysis of risk factors.
Authors: Avinash Pandey, Sushant S. Mittal, Ravi Thippeswamy, Deepan Rajamanickam K., Anant Gokarn, Bharatsinha Baburao Bhosale, Libin Mathew, Sadhna Kannan, Bhausaheb Pandurang Bagal, Jayant Shankar Gawande, Navin Khattry
Journal: Journal of Clinical Oncology (2013)

7043 Background: Engraftment fever (EF) is a phenomenon observed in some patients undergoing autologous transplant (ASCT). We analyzed our data to evaluate the incidence and risk factors associated with EF. Methods: Seventy-nine patients underwent ASCT (53-Hodgkin’s and 26- Non Hodgkin’s) from August 2007 – January 2013. All except 5 received LACE (Lomustine, Ara-C, Cyclophosphamide and Etoposide) conditioning regimen. EF was defined as onset of fever with rising white cell count for which no infectious cause was ascertained. Patients of EF and non-EF groups were compared for the following variables to determine risk factors. These included histology, number of lines of chemotherapy regimens pre-transplant, complete remission (CR) at transplant, peripheral blood CD 34 count on day 1 of collection (PBCD34-D1), CD 34 cell dose collected and infused and number of days of stem cell collection. Results: The median age at transplant was 23.5 years with 57 males and 22 females. Time to neutrophil and platelet engraftment was 10 and 13 days respectively. EF was seen in 35 patients (44 %) at a median of 9 days. Short course of methylprednisolone (n=28) or hydrocortisone (n=3) was given to which all responded. On univariate analysis, PBCD34-D1 &gt; 50/uL (P = 0.037), CD 34 cell dose infused &gt;5.9x10 6 /kg (P=0.012),CD34 cell dose collected &gt; 7.2 x 10 6 /kg (P=0.032) , those receiving ≤ 2 lines of chemotherapy regimens before transplant (P=0.04), those who had ≤ 2 days of stem cell collection (P=0.002) and patients in CR at transplant (P = 0.015) were associated with risk of developing EF. On multivariate analysis, patients in CR at transplant and those who had ≤ 2 days of collection had higher risk of EF. Conclusions: The incidence of EF is high. Patients with lesser days of stem collection and those in CR at transplant have significant risk of developing EF.
Immune compromization and disparities in cancer type among sexual minority men.
Authors: Charles Kamen, Arianna Aldridge Gerry, Michael A. Andrykowski, Oxana Palesh
Journal: Journal of Clinical Oncology (2012)

e16564 Background: Self-identified gay men are at higher risk for contracting HIV and other sexually transmitted infections than their heterosexual counterparts. Gay men are also at higher risk for reporting a lifetime history of cancer diagnoses. While certain types of cancers, specifically Kaposi sarcoma and non-Hodgkin lymphoma, are more common among gay and sexual minority men, it is yet unclear to what extent this disparity is due to immune compromization or comorbid infection with HIV. Methods: The current study utilized data from 173 gay and 5544 heterosexual men collected as part of the Behavioral Risk Factor Surveillance System survey conducted in 2009 in California. Items assessed lifetime history of cancer diagnosis, type of cancer, sexual minority status, and presence of a weakened immune system resulting from diseases such as HIV/AIDS. Chi-square tests were used to examine differences in rates and types of cancer diagnoses by sexual minority status. Logistic regression was then used to examine risk for reporting a lifetime history of cancer based on sexual minority status and accounting for a weakened immune system. Results: In this sample, rates of cancer diagnoses differed significantly between gay and heterosexual men, with gay men more likely to report diagnoses of cancer (χ 2 = 4.53, p &lt; 0.05, OR = 1.53). In addition, types of cancer diagnoses reported differed significantly between gay and heterosexual men, with gay men more likely to report diagnoses of oral cancer (1.2% vs. 0.1%; χ 2 = 23.31, p &lt; 0.001); testicular cancer (1.2% vs. 0.1%; χ 2 = 9.84, p &lt; 0.01); and “other” cancers (1.7% vs. 0.3%; χ 2 = 9.11, p &lt; 0.01). Notably, this disparity in cancer diagnoses persisted even when controlling for a weakened immune system (χ 2 = 3.95, p &lt; 0.05; OR = 1.80, 95% CI = 1.03 to 3.15). Conclusions: Immune system compromization accounts for some of the disparity noted between gay and heterosexual men in rates of cancer diagnoses; however, other risk factors may be implicated. Cancer screening rates for gay men should be increased, and screening physicians should specifically assess for risk factors in gay men.
Impact of clinical parameters on surgical outcomes in patients with hematological disorders undergoing splenectomy.
Authors: Pallawi Torka, Francisco J. Hernandez-Ilizaliturri, Seema Ali Bhat, Myron Stefan Czuczman, Pukhraz Basra, Boris W. Kuvshinoff, George Deeb, Joseph J. Skitzki, Vishala Neppalli
Journal: Journal of Clinical Oncology (2015)

e17689 Background: Safety of splenectomy is of concern in hematological disorders (HD) due to compromised blood indices and platelet dysfunction. Methods: We conducted a retrospective review of clinical parameters and surgical outcomes in splenectomies performed for HD at our institute from 2001 to 2014. Results: Out of 220 splenectomies performed, eighty-six were done for HD (68.6%- lymphoid malignancy, 18.6%-myeloid disorder, 12.8%- benign HD). Open splenectomy (OS) was done in 36% and laparoscopic splenectomy (LS) in 64% of cases (Table 1). Median platelet count was 114,000/µL (4-552,000/µL). Estimated blood loss (EBL) was higher in OS and was not associated with platelet count, spleen size or pathologic diagnosis. Post-op morbidity was 29.1%; higher with OS, less experienced surgeons (<10 procedures), and patients with constitutional symptoms. Median length of stay (LOS) was 6 days (range 2-37 days); longer with high lactate dehydrogenase (LDH), advanced age, low albumin and anemia. 30-day mortality was 7%, with 2.3% deaths attributable to surgical complications. Mortality was higher in patients with myeloid neoplasms, low platelets counts (<50,000/mL), and in those with prior systemic chemotherapy. Massive splenomegaly (>1500gms, N=22) was associated with local symptoms, lower hemoglobin, higher LDH, higher rates of open splenectomy, and a trend towards increased perioperative bleeding. Conclusions: Splenectomy is safe when performed by experienced surgeons in patients with HD. OS was associated with increased perioperative morbidity and mortality. Lower platelet counts were not associated with increased perioperative blood loss or LOS. Comparison between open and laparoscopic splenectomy. Procedure Disease type (%)Lymphoid neoplasms/ Myeloid neoplasms*/ Benign HD Platelet count (per µL) LDH (U/L) Spleen Weight (gram) EBL> 500 ml (%) Post-operative complications (%) LOS(Days) 30-day mortality(%) LS(n=55) 78.1 / 5.4/ 14.5 119.7 ± 89.5 720 ± 350.2 818.2 ± 675.3 20.4 20 5.8 ± 4 1.8 OS(n=31) 51.6 / 29/ 9.6 139.6 ±119.7 1403.9 ± 925.7 1619.8 ± 1019.7 45.2 45.2 8.4 ± 5.9 16.1 p value 0.005 0.4 <0.001 <0.001 0.025 0.025 0.019 0.021 * Exclusion of acute leukemia.
Erlotinib as maintenance therapy after concurrent chemoradiotherapy in patients (p) with stage III non-small cell lung cancer (NSCLC): A Galician Lung Cancer Group phase II study
Authors: J. Casal, S. Vázquez, L. León, M. Lázaro, J. L. Fírvida, M. Amenedo, G. Alonso, L. Santomé, F. J. Afonso
Journal: Journal of Clinical Oncology (2009)

7537 Background: Combination of platinum-based chemotherapy and radiotherapy is the standard treatment for p with unresectable stage III NSCLC, but considering the high rates of recurrence, it is necessary to improve these results. Erlotinib is an EGFR TKI that prolongs survival in p with recurrent and metastatic NSCLC. In this study, we aim to evaluate the role of erlotinib as maintenance therapy after a standard concurrent chemo-radiotherapy regimen in p with stage III NSCLC. Methods: P with unresectable stage IIIA/IIIB—without malignant effusions—NSCLC who had received a standard concurrent chemo-radiotherapy regimen and had no evidence of tumor progression were enrolled in this single arm, open-label phase II study and received erlotinib 150 mg/day po for 6 months. Main eligibility criteria were: PS 0–2, adequate bone marrow, hepatic and renal function and measurable disease by RECIST criteria. Primary endpoint was the percentage of p without evidence of disease progression after 6 months of erlotinib therapy and secondary endpoints were: PFS, OS, ORR and safety profile. Results: 49 p have been included in the study and data from 37 p are presented in this analysis. Baseline characteristics: median age 62 years (range 41–76); male 94.6%; caucasian 100%; smokers/never smokers (%) 97.3/2.7; ECOG PS 0/1/2 (%) 18.9/75.7/2.7; adenocarcinoma/squamous cell carcinoma/large cell carcinoma (%) 16.2/75.7/5.4; stage IIIA/IIIB (%) 16.2/83.8. Most common previous chemo-radiotherapy regimen is cisplatin/docetaxel/RT (83.8%). 27 p were evaluable for tumor response: CR 22.2%; PR 12.8%; SD 55.6%; PD 7.4%. Median TTP was 7.3 months (95% CI 5.8–16.9) and median OS was 18.7 months (95% CI 11.8-NA). Most common adverse events related to erlotinib were rash 30.6% (3 p gr. 3) and diarrhea 16.7%. Conclusions: Erlotinib as maintenance therapy is an active and well tolerated treatment after concurrent chemo- radiotherapy in p with stage III NSCLC. In spite of the majority of patients are caucasian, males, smokers with squamous cell carcinoma, maintenance with single agent erlotinib reached a promising median OS of 18.7 months. Updated data will be presented. No significant financial relationships to disclose.
Tubule-Derived Wnts Are Required for Fibroblast Activation and Kidney Fibrosis
Authors: Dong Zhou, Haiyan Fu, Lu Zhang, Ke Zhang, Yali Min, Liangxiang Xiao, Lin Lin, Sheldon I. Bastacky, Youhua Liu
Journal: Journal of the American Society of Nephrology (2017)

Cell-cell communication via Wnt ligands is necessary in regulating embryonic development and has been implicated in CKD. Because Wnt ligands are ubiquitously expressed, the exact cellular source of the Wnts involved in CKD remains undefined. To address this issue, we generated two conditional knockout mouse lines in which Wntless (Wls), a dedicated cargo receptor that is obligatory for Wnt secretion, was selectively ablated in tubular epithelial cells or interstitial fibroblasts. Blockade of Wnt secretion by genetic deletion of Wls in renal tubules markedly inhibited myofibroblast activation and reduced renal fibrosis after unilateral ureteral obstruction. This effect associated with decreased activation of β-catenin and downstream gene expression and preserved tubular epithelial integrity. In contrast, fibroblast-specific deletion of Wls exhibited little effect on the severity of renal fibrosis after obstructive or ischemia-reperfusion injury. In vitro, incubation of normal rat kidney fibroblasts with tubule-derived Wnts promoted fibroblast proliferation and activation. Furthermore, compared with kidney specimens from patients without CKD, biopsy specimens from patients with CKD also displayed increased expression of multiple Wnt proteins, predominantly in renal tubular epithelium. These results illustrate that tubule-derived Wnts have an essential role in promoting fibroblast activation and kidney fibrosis via epithelial-mesenchymal communication.
<i>DEAR1</i>, a novel tumor suppressor, negative regulator of epithelial-mesenchymal transition, and prognostic factor in non-small cell lung cancer.
Authors: Alfonso Quintas-Cardama, Sean M. Post, Luisa Solis, Shunbin Xiong, Ignacio I. Wistuba, Guillermina Lozano
Journal: Journal of Clinical Oncology (2012)

10506 Background: DEAR1, also known as TRIM62, maps to 1p.35, a genomic interval within which loss of heterozygosity occurs at high frequency in carcinomas. DEAR1 has been proposed as a regulator of cell polarity in vitro. Methods: We genetically engineered mice lacking DEAR1 alleles at murine chromosome 4. To study the impact of DEAR1 loss in lung cancer, DEAR1 deficient mice were crossed to mice carrying the latent mutant K-ras G12D allele (K-ras LA1 ). Results: No survival difference was observed between DEAR1 +/ ─ and DEAR1 ─ / ─ mice (729 vs 699 days, p=0.98) but they were markedly shorter than that of DEAR1 wild-type littermates (803 days, p=0.01). Over 90% of mice developed tumors, mainly adenocarcinomas, including invasive and/or metastatic lung cancer in 23% of cases. DEAR1-deficient K-ras LA1 mice had reduced life span compared with DEAR1 +/+ :K-ras +/LA1 littermates (184 vs 291 days, p&lt;0.0001). The survival of DEAR1 +/ ─ :K-ras +/LA1 and DEAR1 ─ / ─ :K-ras +/LA1 mice were similar (180 vs 153 days, p=0.38) and qPCR and IHC analyses suggested loss of the wild-type DEAR1 allele. The survival of DEAR1-deficient K-ras LA1 mice was also shorter than that of control p53 +/ ─ :K-ras +/LA1 mice (240 days; p=0.01). The metastasis incompetent K-ras LA1 –positive LKR13 cell line after shRNA DEAR1 knock-down and cell lines derived from DEAR1-deficient K-ras LA1 tumors recapitulated an invasive phenotype in transwell migration and 3D culture assays and a metastatic phenotype on SC or IV injection into immunocompetent wild-type littermates. The latter was associated with epithelial-mesenchymal transition involving loss of E-cadherin and DEAR1 expression and upregulation of vimentin, Twist, and CD44. DEAR1 downregulation was very prevalent in a non-small cell lung cancer (NSCLC) tissue array with 214 samples. Patients with early stage NSCLC and loss of DEAR1 expression had a markedly shorter time to relapse compared to those retaining DEAR1 expression (5.1 vs 2.87 years, p=0.049) and worse 5-year relapse-free and overall survival rates. Conclusions: DEAR1 is a novel tumor suppressor that negatively regulates EMT and promotes lung cancer metastasis. DEAR1 loss is a poor prognostic factor in NSCLC.
Phase I expansion study of sunitinib and bevacizumab in patients with advanced solid malignancies.
Authors: Kriti Mittal, Henry B. Koon, Paul Elson, Pierre L. Triozzi, Afshin Dowlati, Ernest C. Borden, Brian I. Rini
Journal: Journal of Clinical Oncology (2013)

e13521 Background: The vascular endothelial growth factor (VEGF) antibody bevacizumab (Bev) and the VEGF receptor (VEGFR) inhibitor sunitinib are efficacious agents in many malignancies. This combination has been previously evaluated in phase I studies of advanced solid tumors. In addition to renal cell carcinoma (RCC), objective responses in the previous phase I occurred in melanoma and adrenal carcinoma. An expansion phase of the phase I study was undertaken primarily to obtain further safety data in these tumor types. Methods: Patients (pts) with metastatic solid tumors with ECOG performance status 0-1 were enrolled on a phase I trial of sunitinib (37.5 mg daily weeks 1-4) and Bev (5 mg/kg iv on days 1, 15 and 29) of a 6 week cycle. Responses were assessed by CT scans performed at baseline and every 12 weeks based on RECIST criteria v1.0. Results: Twenty-two pts were enrolled (10 males, 12 females; median age 58 years) in the expansion cohort. Tumor types included melanoma (11), RCC (5), adrenal cancer (5) and angiosarcoma (1). Prior systemic treatment included chemotherapy (41%) and immunotherapy (27%). Common all grade toxicities included fatigue (77%), hypertension (73%), thrombocytopenia (68%), nausea (59%) and oral mucositis (55%). Grade 3 or higher toxicities occurred in 15 pts (68%); including hypertension (41%), thrombocytopenia (23%) and fatigue (14%). Seven pts developed hemorrhagic events, all grade 1 or 2. Two pts experienced grade 4 thrombocytopenia, 3 RCC pts developed grade 1 thrombotic microangiopathy (TMA); while 1 melanoma patient developed decreased haptoglobin (grade 1) with associated thrombocytopenia (grade 4) and schistocytes consistent with TMA. A median of 2 cycles were completed (range, 1-8). Best response in 19 evaluable pts included partial response 21% (4/19; melanoma (2), adrenal (1), and RCC(1)); stable disease 21% (4/19) and progressive disease 58% (11/19). Overall, 6 pts (31.5%) had measurable reduction in tumor burden. Conclusions: The safety profile of Bev plus sunitinib in melanoma and adrenal carcinoma pts is similar to the previously evaluated toxicities in RCC pts. Although reversible, combined VEGF and VEGFR inhibition may lead to microangiopathy even in non-RCC pts. Clinical trial information: NCT00357318.
The role of multiple coactivators in human matrix metalloproteinase-9 gene expression
Authors: xueyan zhao, Etty Benveniste
Journal: Clinical Cancer Research (2008)

B43  Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase with broad substrates from extracellular matrix proteins to bioactive molecules. It regulates physiological processes such as tissue remodeling and immune responses. However, MMP-9 exacerbates the development of cancers and inflammatory diseases due to its aberrant upregulation. Therefore, MMP-9 has been under intensive study as a cancer therapeutic target. In order to control MMP-9 expression in cancers, understanding the regulatory mechanisms of MMP-9 expression is required. MMP-9 gene expression is regulated mainly at the transcriptional level. In this study, we determined the involvement of multiple transcriptional coactivators in MMP-9 transcription. Our data indicate that coactivators from different groups including CBP/p300, PCAF, CARM1 and GRIP1 are able to activate MMP-9 promoter activity. This enhancement requires the histone acetyltransferase activity of PCAF but not that of CBP/p300, and the methyltransferase activity of CARM1. Furthermore, MMP-9 promoter transcription is synergistically activated by coexpression of p300, CARM1 and GRIP1. This substantial synergy depends on the interaction of p300 and CARM1 with the AD1 and AD2 domains of GRIP1, respectively. These results support the model that these three coactivators form a ternary complex on the MMP-9 promoter. More importantly, these coactivators are associated with the endogenous MMP-9 promoter as shown by chromatin immunoprecipitation assays. SiRNA knockdown of p300, CARM1 and GRIP1 greatly reduced endogenous MMP-9 expression. Collectively, our study illustrates the importance of coactivators for MMP-9 expression, and suggest that knockdown of coactivators is an effective way to decrease MMP-9 expression, which may be particularly useful in breast and prostate cancers, where coactivators are overexpressed.
Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity
Authors: Dongfen Yuan, Xiang Yi, Yuling Zhao, Chi-Duen Poon, Kristin M. Bullock, Kim M. Hansen, Therese S. Salameh, Susan A. Farr, William A. Banks, Alexander V. Kabanov
Journal: Journal of Controlled Release (2017)
Margaret McCartney: Nurses must be allowed to exercise professional judgment
Authors: Margaret McCartney
Journal: BMJ (2017)

As doctors hand over more clinical decisions and responsibility to other healthcare professionals, they need to know that their colleagues can exercise their own professional judgment. A recent decision by the nursing regulator suggests that, for nurses at least, considerable challenges remain.

The Nursing and Midwifery Council (NMC) investigated a complaint brought by a nursing home against one of its staff members. The nurse had “failed to attempt cardiopulmonary resuscitation (CPR)” and “failed to contact or ensure that the emergency services were contacted.”

One of the council’s panels heard that a resident was discovered “waxy, yellow and almost cold.” No “do not resuscitate” order was in place. The facts of what happened otherwise are not …
Coronary Artery Calcification and Risk of Cardiovascular Disease and Death Among Patients With Chronic Kidney Disease
Authors: Jing Chen, Matthew J. Budoff, Muredach P. Reilly, Wei Yang, Sylvia E. Rosas, Mahboob Rahman, Xiaoming Zhang, Jason A. Roy, Eva Lustigova, Lisa Nessel, Virginia Ford, Dominic Raj, Anna C. Porter, Elsayed Z. Soliman, Jackson T. Wright, Myles Wolf, Jiang He
Journal: JAMA Cardiology (2017)

Coronary artery calcification (CAC) is highly prevalent in dialysis-naive patients with chronic kidney disease (CKD). However, there are sparse data on the association of CAC with subsequent risk of cardiovascular disease and all-cause mortality in this population.
Association of body mass index (BMI) with overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC) who received targeted therapies (TT).
Authors: Gargi Surendra Patel, Shahid Ullah, Carol Beeke, Paul Hakendorf, Rob Padbury, Timothy Jay Price, Christos Stelios Karapetis
Journal: Journal of Clinical Oncology (2013)

3592 Background: Preclinical data suggest that adiposity activates pro-inflammatory and insulin-dependent pathways which may lead to resistance to TT, e.g., bevacizumab (Bev) or cetuximab (Cet). Only two retrospective trials have studied the relationship between BMI and outcome for mCRC pts who received TT, with conflicting results. Our aim was to compare OS across BMI groups for mCRC pts treated with TT. Methods: Retrospective data, pertaining to clinical characteristics and outcome, were obtained from the South Australian Registry for mCRC from Feb 2006-Oct 2012. The BMI at first treatment was grouped as Normal (N) = 18.5- &lt;25, Overweight (OW) = 25- &lt;30, Obese I(Ob1) = 30- &lt;35, Obese II (Ob2)≥35. Results: Of 1,174 pts, 39% were OW, 15% Ob1 and 7% Ob2. 352 pts received chemo+TT (Bev, Cet, panitumumab (Pan) and/or regorafenib) and 814 chemo alone. Baseline characteristics were similar across all BMI groups except for type of mCRC: N pts were more likely than obese pts to have synchronous CRC (77.9% vs 56-69.7% for obese). On adjustment for age, sex, synchronous disease, metastatic sites, number of lines of chemo and TT, median OS was longer for N versus OW or Ob1 pts with chemo+TT (35.4 vs 24.9 or 22.7 mons, Table) with no difference in OS for chemo alone. Only N gp pts had an improvement in OS on the addition of TT to chemo. On breakdown by type of TT, OW and Ob1 pts had a poorer outcome with Bev but not with EGFR TT. Conclusions: The BMI is an independent predictor for a poorer outcome for OW and OB1 pts with chemo+TT, specifically for pts receiving Bev. The OW and OB1 patients may be a target group for lifestyle and nutrition advice to improve OS with TT. Prospective studies are required to validate this finding. [Table: see text]