tbuckley/cabot-search huggingface dataset:
High-dose cisplatin combination chemotherapy in the treatment of advanced epithelial ovarian carcinoma.
Authors: J D Hainsworth, L S Burnett, H W Jones, W W Grosh, D H Johnson, F A Greco
Journal: Journal of Clinical Oncology (1990)

We treated 25 newly diagnosed patients with advanced epithelial ovarian cancer with an intensive induction chemotherapy regimen using high-dose cisplatin in combination with cyclophosphamide and doxorubicin. All patients had either stage IIIC or stage IV disease. Two intensive induction courses of chemotherapy were administered at 28-day intervals, which consisted of cisplatin 40 mg/m2 daily for 5 days, cyclophosphamide 500 mg/m2 day 1, and doxorubicin 40 mg/m2 day 1. Four courses of chemotherapy using cisplatin 60 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 500 mg/m2 followed the high-dose induction therapy. Two of the first six patients died during high-dose induction therapy (one died of neutropenia and sepsis, one of intercurrent intracerebral hemorrhage). Doxorubicin was subsequently omitted from the induction therapy due to unacceptable myelosuppression; no deaths occurred in the remaining 19 patients, and myelosuppression was manageable. Peripheral neuropathy was the most severe side effect with this regimen. This complication was unpredictable, developed during the third or fourth month of treatment, and was disabling in five patients. Other toxicity included prolonged nausea and vomiting (eight patients), ototoxicity (five patients), and nephrotoxicity (two patients), but these did not compromise therapy. All 23 assessable patients had objective response to therapy. Four of 12 patients who underwent second-look laparotomy had pathologic complete response, while four additional patients had only microscopic residual disease. The median survival for the entire group was 25 months. Four patients remain continuously disease-free 23 to 48 months following completion of therapy. Although this regimen was tolerated by most patients, the unpredictable occurrence of disabling neuropathy may limit its usefulness.(ABSTRACT TRUNCATED AT 250 WORDS)
Suicide internalized: an existential sequestrum
Authors: E K Rynearson
Journal: American Journal of Psychiatry (1981)

Suicidal bereavement involves more than the personalized reaction to the death of another. The bereaved is also left with the cognitive and emotional dilemma of death as a chosen option for existence. This existential contradiction creates enduring changes in cognitive and emotional perspective. The author reviews these changes and their therapeutic implications.
Recommended guidelines for the treatment of chemotherapy-induced diarrhea.
Authors: S Wadler, A B Benson, C Engelking, R Catalano, M Field, S M Kornblau, E Mitchell, J Rubin, P Trotta, E Vokes
Journal: Journal of Clinical Oncology (1998)

PURPOSE Management of chemotherapy-induced diarrhea (CID) has customarily involved symptomatic treatment with opioids in conjunction with supportive care. Alternatively, patients refractory to conventional therapy have been given octreotide, a somatostatin analogue. Although this agent has been effective against CID, no widely accepted treatment guidelines that incorporate its use currently exist. An expert multidisciplinary panel was convened to formulate clinical practice guidelines for the treatment of CID. METHODS The panel reviewed clinical data on the management of CID reported in the literature and analyzed currently available tools used to assess CID. Expert consensus was applied when published data were insufficient. Panel members also considered the effect of CID on quality of life and the cost-effectiveness and efficacy of different pharmacologic approaches. Effective resolution of CID and decreases in the need for supportive care or hospitalization were considered to be primary goals in the formulation of the guidelines. RESULTS The panel formulated suggested practice guidelines for the management of CID that detail recommendations for the assessment and evaluation of diarrhea and the sequence and duration of administration of specific pharmacologic agents. CONCLUSION The consensus of the panel was that standardized assessment and management of diarrhea is required to effectively control CID. The panel agreed that further data from a National Cancer Institute (NCI)-sponsored intergroup trial is required to determine the optimal dosage of octreotide and its cost in the treatment of cancer. The panel also agreed that further clinical research is warranted to address significant questions about the most effective way to assess and treat CID.
An Epithelioid Variant of the BHK21 Hamster Fibroblast Line and Its Transformation by Polyoma Virus&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: L Montagnier, I MacPherson, O Jarrett
Journal: JNCI Journal of the National Cancer Institute (1966)

An epithelioid variant, which forms characteristic colonies in soft agar medium, has been isolated From the BHK21/13 line of hamster Abroblasts. After infection with a high multiplicity of polyoma virus, a fraction of the cells is morphologically transformed. Transformation may be demonstrated in two ways: 1) When infected cells are grown on glass, dense colonies of transformed cells develop from the confluent monolayer of untransformed cells in which multiplication has stopped because of their contiguity. 2) In agar, colonies derived from transformed cells are larger and morphologically distinct from those Formed by the untransformed cells. The variant cells produce tumors in hamsters. Their transplantability is increased by polyoma transformation. Transformed cells possess a new polyoma-specific cell antigen.
Dinosaurs among us causing chaos and confusion
Authors: Adam Meakins
Journal: British Journal of Sports Medicine (2015)

The recent Hollywood blockbuster Jurassic World tells a story of how extinct species have returned to the present only to cause chaos and confusion. Unfortunately, this Hollywood fantasy is a reality within the world of physiotherapy with dinosaurs among us causing chaos and confusion.

The dinosaurs I am referring to are the many iconic, influential and idolised clinicians and researchers who, despite a new era in understanding pain and growing evidence of the biopsychosocial model, still stubbornly refuse to change their methods or mind-set, and continue to promote and teach outdated methods of assessment and treatment.

The dinosaurs, despite giving occasional lip service to the biopsychosocial paradigm, have no desire to support or promote it. They have vested interests in peddling snake oil treatments, and selling their courses and books that promise simple assessments and quick fixes, from realigning subluxed sacroiliac joints or twisted thoracic rings, to releasing psoas muscles or immobile kidneys.

The dinosaurs continue to worship predominantly at the altar of biomechanics and in the normalising of movement. They continue to teach the identification and correction of incomprehensibly subtle joint and muscle imbalances, …
OP04 Circulating levels of the long pentraxin PTX3, but not hepatocyte derived C-reactive protein, correlate with severity following human acute liver injury
Authors: D Craig, P Lee, E A Pryde, S Walker, G Beckett, P Hayes, K Simpson
Journal: Gut (2010)

Introduction  The innate immune response may underpin the development of multiorgan failure following acute liver injury, particularly following paracetamol overdose (POD). Pentraxin 3 (PTX3) is a long pentraxin induced by interleukin (IL)-10, and produced by vascular endothelium, macrophages, and myeloid dendritic cells. PTX3 has diverse effector functions including opsonisation, clearance of apoptotic debris, and tissue repair.  Aim  To measure levels of PTX3 and C-reactive protein (CRP), a hepatocyte derived short pentraxin involved in the acute phase response, in patients with acute liver injury.  Method  Consecutive patients admitted to the Royal Infirmary of Edinburgh with acute liver injury (ALT>1000 IU/l and coagulopathy) were enrolled. PTX3 and CRP levels were measured by ELISA and turbimetry, respectively.  Results  A total of 60 patients (48 POD, 12 non-POD) were enrolled. 28/48 (58.3%) of POD and 8/12 (66.7%) non-POD patients developed hepatic encephalopathy (HE), and therefore acute liver failure. As expected, admission PTX3 levels correlated strongly with IL-10 (Spearman9s r=0.641, p  Conclusion  These data suggest that the humoral arm of the innate immune system plays an important role in the pathogenesis of multiorgan failure following POD. PTX3 may have a role as a novel prognostic marker in this condition.
Inhibition of Human Breast Carcinoma Growth by a Soluble Recombinant Human CD40 Ligand
Authors: Akio Hirano, Dan L. Longo, Dennis D. Taub, Douglas K. Ferris, Lawrence S. Young, Arisitides G. Eliopoulos, Angelo Agathanggelou, Nicky Cullen, James Macartney, William C. Fanslow, William J. Murphy
Journal: Blood (1999)
Multimodal salvage therapy for locally recurrent and re-recurrent rectal cancer.
Authors: Y. You, E. A. Choi, J. M. Skibber, M. A. Rodriguez-Bigas, B. W. Feig, C. Eng, C. H. Crane, P. Das, G. J. Chang
Journal: Journal of Clinical Oncology (2010)

3647 Background: Radical salvage surgery offers the only chance of potential cure for locally recurrent rectal cancer (LRRC). We examined predictors of outcome after multimodality salvage for LRRC and determined outcomes after secondary failure. Methods: A retrospective consecutive cohort study of patients (pts) undergoing surgical salvage for LRRC between 1988 and 2008 was conducted. Only pts who underwent radical resection for their primary rectal tumors were included. Cox regression analysis was performed to evaluate survival outcomes. Results: A total of 171 pts were identified. Median age was 59 years (interquartile range [IQR] 47-67); 97 pts (57%) were male. Salvage for LRRC required repeat rectal resection in 80 (47%), exenteration in 63 (37%), and radical pelvic tumor excision in 28 (16%) pts. Bone resection was needed in 50 (29%). The rate of R0 resection was 79%. Radiation was used in 109 (67%) prior to salvage, including 43 (47%) who had received prior pelvic radiation. Intraoperative radiotherapy was given to 57 (33%) and postoperative chemotherapy, to 48 (28%). At 5 years, overall survival (OS) was 42% and recurrence-free survival was 30%. Secondary failure occurred in 94 (55%) after a median interval of 11 months from salvage operation. The site of first failure was local only in 44 (25%), distant only in 33 (19%), both in 5 (3%). Second operative salvage was undertaken in 26 (28%) pts, including repeat pelvic resection in 21 (81%). Other treatments included chemotherapy, reirradiation, and brachytherapy. The 5-year OS with secondary failure was 37% (vs. 50% without failure; p = 0.036), but pts who underwent repeat salvage operation had significantly higher OS than those who did not: 46 vs. 33% (p = 0.049). In multivariate analysis, independent predictors of improved OS included: R0 resection margin status (p = 0.01) and recovery of lymph nodes during salvage surgery (p = 0.027). Conclusions: Prolonged survival and local control can be achieved by multimodality salvage therapy for LRRC. Repeat salvage after secondary failure is appropriate in select patients. Finding residual lymph nodes at salvage operation may suggest incomplete mesorectal resection at primary rectal cancer resection which correlated with improved salvageability. No significant financial relationships to disclose.
Intermittent hepatic arterial infusion of high-dose fluorouracil on a weekly schedule as adjuvant chemotherapy following curative resection of colorectal liver metastases: a randomized study
Authors: T. Tono, T. Ukei, T. Kanoh, T. Ohnishi, S. Masutani, K. Shibata, T. Monden
Journal: Journal of Clinical Oncology (2005)

3727 Background: More than half of patients received curative resection of liver metastases from colorectal carcinoma develops recurrent disease in the residual liver. The authors have reported the efficacy of short-term hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) in preventing the hepatic recurrence (Cancer 88: 1549, 2000). In this paper the usefulness of intermittent HAI chemotherapy of high dose 5-FU on a weekly schedule was investigated. Methods: Thirty-eight patients were randomly assigned into 2 groups. Nineteen patients received 1500 mg of 5-FU intra-arterially for 5 h once a week for 8 weeks (WH-HAI group). AS a control, the remaining 19 cases received continuous infusion of 5-FU (500 mg/d) for 4 days (96h) per week in 6 weeks (C-HAI group). The latter regimen had been established in our previous study. In both protocols, the total dosage of 5-FU was 12g, and the treatment was performed using disposable infusion pumps. Results: In terms of the patient characteristics including age, sex, Dukes’ stage, tumor size, chronology, number of tumor, location of tumor and type of hepatectomy, there was no statistically significant difference between the two groups. The median follow-up period was 47.4 months. The recurrence was confirmed in 12 cases of each group, and, of those, 4 patients of each group had recurrent disease in the residual liver. The 1-, 2-, 3-year hepatic disease free survival were 80, 74 and 74% in WH-HAI group, respectively, and 83, 78 and 78%, in C-HAI group, respectively (p=0.7989). No patients of either group suffered any adverse effect of Grade 3 or more. Five cases of WH-HAI group and 6 from C-HAI group were dead of disease. The 1-, 3- and 5-year cumulative survival of WH-HAI group were 90, 78 and 78%, respectively, whereas those of C-HAI group were 100, 68 and 68%, respectively (p=0.9237). Conclusions: As an adjuvant chemotherapy following curative resection of colorectal liver metastases, a new weekly administration of high-dose 5-FU regimen, which seems more simple and convenient, showed a similar effect to continuous HAI protocol in preventing the hepatic recurrence without any serious complication. No significant financial relationships to disclose.
Prognostic factors for relapse in stage I seminoma managed with surveillance: A validation study.
Authors: P. W. Chung, G. Daugaard, S. Tyldesley, T. Panzarella, C. K. Kollmannsberger, M. K. Gospodarowicz, P. R. Warde
Journal: Journal of Clinical Oncology (2010)

4535 Background: A prognostic model for stage I seminoma managed by orchiectomy alone has limited predictive value since the high risk group has only a 30% relapse rate. Although the model has not been validated in an independent data set, it has been applied widely in treatment policies. We tested the value of the model in a consecutive series of patients managed by surveillance in the past decade. Methods: Individual data on 687 stage I seminoma patients managed by surveillance between 1998 and 2005 at the Copenhagen National Hospital, Princess Margaret Hospital and British Columbia Cancer Agency was retrospectively analyzed. Impact of age at diagnosis, original pathology [tumor size, histologic subtype, rete testis invasion, epidydimis, extratesticular soft tissue, spermatic cord, tunica albuginea, and small vessel invasion (SVI)] were analyzed for prognostic importance for relapse. The analysis was limited by missing data in significant proportion of reports [rete testis (33%), SVI (25%), tumor size 21%)]. Results: The current series had significantly smaller tumors (median size 3 cm vs. 4cm in previous data, p< 0.001) but no significant differences in the other factors examined. With a median follow-up of 3.85 years, 88 patients have relapsed for an actuarial 5-yr relapse-free rate of 85%. On univariate analysis, tumor size, treated as a continuous variable, was the only factor to predict for relapse (p=0.0049). We tested the published factors: tumor size (≤ 4cm vs. > 4cm) and rete testis invasion. In the current data set neither factor reached statistical significance in multivariate analysis: tumor size HR 1.36, (95% CI 0.80, 2.36); rete testis invasion HR 1.16, (95% CI 0.69, 1.96). Conclusions: While tumor size retained prognostic importance, even with smaller tumors in this series, we have been unable to validate the previously developed prognostic model for relapse on seminoma surveillance. This confirms our previous impression that with a low failure rate, it is unlikely that clinical factors will yield much more valuable information than described to date. Future studies of molecular tumour characteristics/gene signature and/or improved imaging may refine the approach to the management of stage I seminoma. No significant financial relationships to disclose.
Abstract 18626: A Novel Inhibitory Role of MicroRNA-1 in Cardiac Fibroblast Proliferation and Differentiation
Authors: Michelle E King, Peng Zhang
Journal: Circulation (2013)

Fibroblasts play a key role in cardiac remodeling by differentiating into myofibroblasts, proliferating and producing excess extracellular matrix. MicroRNAs (miRs) are important regulators in cardiac development and disease. To date, miR analyses have been performed mostly in myocytes and cardiac tissue; little is known about miRs in cardiac fibroblasts. Using miR arrays, we determined the expression and regulation of miRs in adult rat ventricular fibroblasts in a culture model that mimics the phenotypic and functional changes of fibroblasts in diseased heart. Among miRs that were dynamically regulated, we found that miR-1, a muscle-enriched miR that has so far been extensively studied in myocytes, is expressed in fibroblasts and markedly downregulated (~10-fold) upon activation. MiR-1 downregulation was also observed in fibroblasts stimulated with angiotensin II or TGFβ for 48 hours. Gain-of-function studies in cultured rat ventricular fibroblasts showed a dose-dependent inhibitory effect of miR-1 on fibroblast proliferation (3- and 26-fold overexpression led to a 13% and 34% reduction, respectively). In contrast, fibroblast proliferation was significantly increased by 20% when endogenous miR-1 was only knocked down by 40%. Similar changes were observed in fibroblasts subjected to angiotensin II and TGFβ. Using immunostaining, we found a marked reduction of α-smooth muscle actin expression by miR-1, indicating an inhibitory effect of miR-1 on fibroblast differentiation. Mechanistic studies showed miR-1-dependent regulation of protein expression of several putative miR-1 targets that are involved in initiation of cell cycle progression (e.g., cyclin D2, CDK6) and fibrosis development (e.g., PKCε, HDAC4), some of which have been confirmed for miR-1 targeting by 3’-UTR luciferase reporter assays. Together, we show dynamic regulation of miRs in cardiac fibroblasts upon activation and demonstrate a novel inhibitory role of miR-1 in cardiac fibroblast proliferation and differentiation. Our data suggest a potential anti-fibrotic effect of miR-1 overexpression in fibroblasts and highlight the importance of cell type-specific miR-1 modulation, given the potential for arrhythmia induction reported for miR-1 overexpression in myocytes.
Predictive value of baseline CD66e/CEA serum levels on efficacy of bevacizumab-based treatment in advanced colorectal cancer.
Authors: Gerald W. Prager, Kira H. Bramswig, Christoph Zielinski
Journal: Journal of Clinical Oncology (2013)

388 Background: CD66e (Carcinoembryonic antigen, CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor-angiogenesis. This study aimed to evaluate baseline CD66e serum levels as response predictor to bevacizumab-based therapies in patients with metastatic colorectal cancer (mCRC). Methods: 298 patients with mCRC and first-line treatment were analyzed. 169 mCRC received bevacizumab plus chemotherapy and 129 patients with mCRC treated with cetuximab (KRAS w.t.) and identical chemotherapy (FOLFOX6 or FOLFIRI). Disease control (DC), progression-free survival (PFS) as well as overall survival (OS) were assessed and related to baseline CD66e-serum levels. Patients with basal CD66e-serum levels below the statistical median of 26.8 ng/ml (group I) were compared with patients with higher CD66e levels (group II). Results: Baseline CD66e serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (chi square i&lt;0.005: OR=0.579, 95% C.I. 0.422, 0.795; p&lt;0.001), inversely correlated with median PFS leading to a median PFS benefit of 2.1 month for patients in group I when compared with group II (p&lt;0.05), as well as inversely correlated with median OS (37.5 month vs. 21.4 month, p&lt;0.05). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CD66e serum levels was found (p&gt;0.05). Conclusions: These data give first evidence of CD66e as a predictive biomarker for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.
A prospective study of various regimens using external radiation therapy and HDR brachytherapy in locally advance carcinoma cervix
Authors: M. Nagarajan, V. Nagarajan, N. R. Tulasi
Journal: Journal of Clinical Oncology (2005)

5176 Background: External Radiation therapy and Brachytherapy remains to be the mainstay of treatment in locally advanced Carcinoma Cervix for local control with (or) without chemotherapy. Methods: From June 2000 to August 2002, 55 patients were enrolled in a study to evaluate the various regimens of external radiation therapy and HDR Brachytherapy with (or) without platinum based chemotherapy. External radiation therapy of 50 - 60 Gy was delivered by Telecobalt Co-60 Theratron machine by 4 field box technique. After 2 weeks of rest of the last external radiation therapy patients received Brachytherapy by Nucletron Microselectron HDR machine with Nucletron GYN Applicator, 5 - 8 Gy/ fraction x 2 fractions to point A depending on the bladder and rectal dose was delivered. Results: One patient defaulted for treatment. 38 patients received 60 Gy eq; 14 patients 50 Gy eq; 1 patient each 54 Gy and 56 Gy eq by external Radiation therapy. IV/IU was done in 44 patients; IU+Dobbies was done in 10 patients. The Bladder dose by Brachytherapy was 100% in 6 patients. The Rectal dose by Brachytherapy were < 40% in 1 patient; 41 - 60% in 10 patients; 61–80% in 31 patients; 81–100% in 11 patients and > 100% in 1 patient. Total doses were 1 patient had 62 Gy eq; 3 patients had 70 Gy eq; 2 patients had 72 Gy eq; 2 patients had 74 Gy eq; 37 patients had total doses 76 Gy eq; 4 patients had 78 Gy eq; 4 patients 80 Gy eq and 1 patient had 85 Gy eq. Response and Survival: 4(7.5%) Patients had residual disease. 6 (11%) patients had local recurrence. 3 (6%) patients had nodal failure. 3 (6%) patients had distant failure. The follow-up ranged from 24 months to 51 months, The average disease free survival was 22 months and average overall survival was 31 months. Toxicity: One patient had Grade IV bladder toxicity, 2 patients had Grade I and 1 patient had Grade II rectal toxicities.Conclusion: External radiation dose of 60 Gy in 30 fractions by 4 field box technique, 200 c Gy/fraction, 5 days a week followed by 2 fractions of HDR Brachytherapy of 5 - 7 Gy/fraction depending on the bladder and rectal dose with (or) without chemotherapy gives a good local control of 82% at 2 years for locally advanced Carcinoma Cervix. The bladder and rectal toxicities were acceptable. No significant financial relationships to disclose.
Nobel awarded to discoverers of ivermectin and artemisinin
Authors: Geoff Watts
Journal: BMJ (2015)

The 2015 Nobel prize for physiology or medicine has been awarded to three researchers whose work has had a huge effect on the treatment of parasitic diseases that affect many millions of people in poor countries.

One half of the prize goes jointly to William Campbell, emeritus research fellow at Drew University in Madison, New Jersey, and Satoshi Omura, professor emeritus at Kitasato University in Japan, “for their discoveries concerning a novel therapy against infections caused by roundworm parasites.” The agent they discovered was avermectin, later chemically modified to create the drug now in widespread use, ivermectin.

The second half of the prize went …