tbuckley/cabot-search huggingface dataset:
Lymphoproliferative Responses in Recrudescent Orofacial Herpetic Infections
Authors: J P Vestey, M Norval, S E M Howie
Journal: Journal of the Royal Society of Medicine (1990)

The relationship between antibody (Ab) and lympho-proliferative responses to herpes simplex virus (HSV) and recrudescent orofacial HSV lesions were investigated in 65 patients. All had HSV-specific Ab and cell mediated immune responses (CMIR) demonstrated by ELISA and in vitro lymphoproliferation respectively. Thirteen control subjects were negative in both tests. Thirty-three patients were repeatedly investigated for 6-38 months during which time they suffered 1-8 recrudescences. HSV-induced lymphoproliferation was depressed during recrudescences, rose to a peak several weeks later, and declined slowly to a background level. However, ELISA titres and lymphoproliferative responses to Concanavalin A (Con A) were high throughout and circulating peripheral blood mononuclear cell (PBMC) subsets did not change. Depressed lymphoproliferative responses to HSV antigen (Ag) during recrudescences were enhanced by removal of CD8+ cells from PBMC using either a panning technique or cell sorting; reconstitution of CD8+ cells suppressed the HSV-specific lymphoproliferative response. CD8+ cell depletion affected neither HSV-induced lymphoproliferation recrudescence, nor lymphoproliferative responses to another Ag (PPD) during recrudescence. Depressed HSV-induced lymphoproliferation during recrudescences might thus be due to CD8+ suppressor T cell (Ts) function rather than low numbers of circulating lymphocytes. Suppression or delay of normal CMIR to asymptomatic recurrent epidermal HSV infection by Ts might allow development of recrudescent HSV lesions.
Anti-cancer activity of N-heterocyclic indolyl glyoxylamides
Authors: Jiunn Jye Chuu, Chiung Tong Chen
Journal: Cancer Research (2004)

5137   We have recently reported a series of novel orally active anti-cancer compounds,  N -heterocyclic indolyl glyoxylamides (Li et al.,  J. Med. Chem.  2003). These synthetic compounds were previously shown active against the in vitro growth of several cancer cells, in inducing cancer cell apoptosis and in prolonging the survival of leukemic mice in vivo. In the present study, we further looked into the mechanisms by which these synthetic analogues act on cancer cells in in vitro as well ex vivo histoculture models. The results showed that four tested analogues exhibited a potent and concentration-dependent cytotoxicity in human gastric cancer MKN45 cells (IC50= 0.007-0.082 μM) by the sulforhodamine B assay. Accordingly, they were active (IC50= 0.012-0.052 μM) against the proliferation of tumor cells in histocultured MKN45 xenograft tumors treated for 96 hr measured by bromodeoxyuridine incorporation. Two of them showed an anti-proliferation activity similar to that of paclitaxel treatments. In the histocultured MKN45 xenograft tumors, these compounds also induced apoptosis (EC50= 0.173-0.775 μM) detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay indicating that the in vitro cytotoxicity is partly attributable to apoptotic cell death. Furthermore, an in vitro tubulin polymerization (turbidity) assay demonstrated that these synthetic anti-cancer agents inhibited tubulin assembly (IC50 = 0.27-5.70 μM). Our findings indicated that the novel  N -Heterocyclic indolyl glyoxylamides may exert cytotoxic activity via induction of apoptosis in human gastric carcinomas and that unbalance in the microtubule kinetics may be one of the mechanisms of apoptotic induction.
Main and additional predictors of COPD progression
Authors: Luydmyla Konopkina, Bogdana Basina
Journal: European Respiratory Journal (2014)

Aim:  to determine the significance of different parameters as predictors of COPD progression.   Methods:  74 patients with verified stable COPD (age – 62,1±0,91 years, men – 68 (91,9 %), women – 6 (8,1%)), divided into two subgroups: 1 – 37 (50,0%) patients with mild COPD (GOLD I and II), 2 – 37 (50,0%) patients with severe COPD (GOLD III and IV). Statistical analysis (Bayes theorem and Vald9s serial (sequential) analysis with calculation of Kulbak9s information measure) of 24 parameters: demographic, anamnestic, questionnaire, clinical, functional, laboratory. Prognostic threshold for hypotheses of COPD progressing presence was diagnostic ratio (DR) of +13, and for the hypothesis of absence – the DR of -13.   Results:  main criteria for the risk of COPD progression are spirometric factors as FEV1(post) (in gradations of ≤55 (DR is +14) and ≤60% pred. (DR is +7)), FEV1(pre) (in gradations of ≤50 (DR is +12) and ≤45% pred. (DR is +13)) and the ratio FEV1/FVC in gradations ≤0,45 as in the pre-dose (DR is +6) like in post-dose (DR is +7). Additional criteria for COPD progressing are other parameters (patient9s age over 65 years (DR is +4), active tobacco smoking and ex-smokers over 39 pack/years (DR is +2), the number of points on the scale impact according SGRQ more than 60 (DR is +7), plasma levels of C-reactive protein more than 7,4 mg/l (DR is +3)).   Conclusions:  at determining the risk of COPD progression the levels of lung function during spirometry should be first done; if the impossibility of spirometry additional studies should be done with count of prognostically significant, taking into account this and some demographic and medical history data.
Multiple myeloma: VMCP/VBAP alternating combination chemotherapy is not superior to melphalan and prednisone even in high-risk patients.
Authors: M Boccadoro, F Marmont, M Tribalto, G Avvisati, A Andriani, T Barbui, M Cantonetti, M Carotenuto, B Comotti, F Dammacco
Journal: Journal of Clinical Oncology (1991)

The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P less than .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v 37.0 months, P less than .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m greater than or equal to 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to MP.
Hematopoietic Colony-Forming Units in Mice Infected by the Polycythemia-Inducing Friend Virus. III. Pattern of Blood Recovery in Irradiated Mice Grafted With Normal or Infected Spleen Cells
Authors: Françoise Wendling, P. E. Tambourin, P. Jullien
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Hematopoietic Colony-Forming Units in Mice Infected by the Polycythemia-Inducing Friend Virus. III. Pattern of Blood Recovery in Irradiated Mice Grafted With Normal or Infected Spleen Cells Get access Françoise Wendling, Françoise Wendling Unité de Physiologie Cellulaire, Institut National de la Sante et de la Recherche Medicale, Institut du Radium, 91405 Orsay, France Search for other works by this author on: Oxford Academic PubMed Google Scholar P. E. Tambourin, P. E. Tambourin Unité de Physiologie Cellulaire, Institut National de la Sante et de la Recherche Medicale, Institut du Radium, 91405 Orsay, France Search for other works by this author on: Oxford Academic PubMed Google Scholar P. Jullien P. Jullien Unité de Physiologie Cellulaire, Institut National de la Sante et de la Recherche Medicale, Institut du Radium, 91405 Orsay, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 51, Issue 1, July 1973, Pages 179–189, https://doi.org/10.1093/jnci/51.1.179 Published: 01 July 1973 Article history Received: 19 December 1972 Accepted: 16 March 1973 Published: 01 July 1973
Phase I clinical and pharmacologic study of intraperitoneal cisplatin and fluorouracil in patients with advanced intraabdominal cancer.
Authors: R L Schilsky, K E Choi, J Grayhack, D Grimmer, C Guarnieri, L Fullem
Journal: Journal of Clinical Oncology (1990)

Fluorouracil (5-FU) and cisplatin display marked therapeutic synergy in preclinical models and are effective in the treatment of a number of solid tumors when combined and administered intravenously (IV). Each drug has also been administered intraperitoneally (IP) and displays a favorable pharmacologic profile and acceptable clinical toxicity. We therefore undertook a phase I study to determine the feasibility and toxicity of combination IP chemotherapy with these agents. Thirty-one patients with histologically documented malignancy confined to the peritoneal space were treated with cisplatin 90 mg/m2 mixed with 5-FU in 2 L of lactated Ringer's solution and given IP for 4 hours every 28 days. Cohorts of at least three patients received starting 5-FU concentrations ranging from 5 mmol/L (1,300 mg in 2 L) to 20 mmol/L. The dose-limiting toxicity was neutropenia with a median granulocyte nadir of 156 cells per microliter occurring at a 5-FU dose of 20 mmol/L. Intrapatient escalation of the 5-FU dose was permitted and 15 cycles of chemotherapy were delivered at 5-FU concentrations greater than 20 mmol/L, the highest concentration being 30.7 mmol/L (8 g of 5-FU in 2L). Other toxicities included mild to moderate nausea during all cycles of therapy, vomiting in 54% of cycles, and diarrhea in 15% of cycles. Abdominal pain, renal dysfunction, peripheral neuropathy, and oral mucositis occurred infrequently and were not related to the 5-FU dose. Peritoneal fluid and plasma 5-FU concentrations were measured by high-performance liquid chromatography (HPLC) in selected patients. Mean peak plasma 5-FU concentrations ranged from 6.19 mumol/L to greater than 60 mumol/L, and peritoneal fluid to plasma 5-FU area under the curve (AUC) ratios ranged from 85 to 1,150. Nine of 15 patients with nonbulky disease had resolution of malignant ascites or at least a 50% reduction of peritoneal studding by tumor at repeat laparotomy. We conclude that combination IP chemotherapy with cisplatin and 5-FU is technically feasible and has acceptable clinical toxicity and a favorable pharmacologic profile. The recommended starting 5-FU dose for phase II trials is 3,900 mg mixed with 90 mg/m2 of cisplatin in 2 L of isotonic fluid.
Brief Communication: Conversion of Nitrosobenzene to N -phenylacetohydroxamic Acid by Yeast Pyruvate Decarboxylase 2
Authors: Michael D. Corbett, Jean E. Cahoy, Bernadette R. Chipko
Journal: JNCI Journal of the National Cancer Institute (1975)

In the presence of yeast enzyme concentrate or purified yeast pyruvate decarboxylase, nitrosobenzene was converted in part to N-phenylacetohydroxamic acid. This transformation had to be catalyzed by the enzyme, since the incubation of nitrosobenzene with the cofactor of pyruvate decarboxylase did not produce the hydroxamic acid. Similar incubations conducted with phenylhydroxylamine did not yield any detectable amounts of N-phenylacetohydroxamic acid.
Long-Term Cultivation in Tissue Culture of Leukemic Cells From Mouse Leukemia Induced by Moloney Virus or by X Rays&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Haim Ginsburg, Leo Sachs
Journal: JNCI Journal of the National Cancer Institute (1961)

Successful long-term in vitro cultures of leukemic cells have been obtained from BALB/c, C57BL/6, SWR, and Swiss mice, with leukemia induced by Moloney virus; and from C57BL/6 mice, with leukemia induced by X rays. The leukemic cells were grown from 4 to 10 months in vitro. All the cell lines were successfully maintained on feeder layers of normal mouse spleen cells in Eagle's medium supplemented with horse serum. Under these conditions the leukemic cells grew free in the medium, so that they could be readily passaged without trypsinization. The leukemic nature of the cultured cells was established by examination of cell smears and by cell transplantation into animals.
Expression of the bile acid receptor FXR in Barrett's esophagus and enhancement of apoptosis by guggulsterone in vitro.
Authors: Andrea De Gottardi, Jean-Marc Dumonceau, Fabien Bruttin, Alain Vonlaufen, Isabelle Morard, Laurent Spahr, Laura Rubbia-Brandt, Jean-Louis Frossard, Winand NM Dinjens, Peter S Rabinovitch, Antoine Hadengue
Journal: Molecular Cancer (2006)

Barrett's esophagus, a risk factor for esophageal adenocarcinoma, is associated with reflux disease. The aim of this study was to assess the expression of bile acid receptors in the esophagus (normal, esophagitis, Barrett's esophagus and adenocarcinoma) and to investigate their possible function. the expression of the bile acid receptors FXR and VDR in esophageal biopsies from patients with a normal mucosa, esophagitis, Barrett's esophagus or adenocarcinoma (n = 6 per group) and in cell lines derived from Barrett's esophagus and esophageal adenocarcinoma, was assessed by real time Q-PCR and immunohistochemistry. The effect of guggulsterone, an antagonist of bile acid receptors, on apoptosis of Barrett's esophagus-derived cells was assessed morphologically, by flow cytometry and by measuring caspase 3 activity. The expression of FXR was increased in esophagitis, Barrett's esophagus and adenocarcinoma compared to normal mucosa by a mean of 44, 84 and 16, respectively. Immunohistochemistry showed a weak expression in normal esophagus, a strong focal reactivity in Barrett's esophagus, and was negative in adenocarcinoma. VDR expression did not significantly differ between groups. In cell cultures, the expression of FXR was high in Barrett's esophagus-derived cells and almost undetectable in adenocarcinoma-derived cells, whereas VDR expression in these cell lines was not significantly different. In vitro treatment with guggulsterone was associated with a significant increase in the percentage of apoptotic cells and of the caspase 3 activity. the bile acid receptor FXR is significantly overexpressed in Barrett's esophagus compared to normal mucosa, esophagitis and esophageal adenocarcinoma. The induction of apoptosis by guggulsterone in a Barrett's esophagus-derived cell line suggests that FXR may contribute to the regulation of apoptosis.
A new mutation of surfactant protein C gene causing severe respiratory insufficiency and pulmonary fibrosis
Authors: Francesca Petreschi, Teresa Salerno, Donatella Peca, Maria Beatrice Chiarini Testa, Alessandra Schiavino, Maria Giovanna Paglietti, Olivier Danhaive, Renato Cutrera
Journal: European Respiratory Journal (2012)

The pulmonary surfactant is an unique phospholipid and protein complex that is synthesized, packaged and secreted by alveolar type II cells. The phospholipid compontents constitute approximately 90% weight of pulmonary surfactant, while the remaining 10% is constituted by protein components, including surfactant-associated proteins SP-A, B, C and D. Genetic mutations in surfactant production and function are associated with different clinical phenotypes and can cause significant primary lung disease in full-term infants, older children and adults.  Mutations in the surfactant protein C gene have been recently associated with the development of diffuse lung disease, particularly sporadic and familial interstitial lung disease.  SC is a one year old girl, who presented acute respiratory insufficiency at 6 months of age during an acute bronchiolitis, requiring intubation and mechanical ventilation. CT scan showed bilateral ground glass appearance and siderocytes were found in BAL fluid. She was referred 6 months later in poor general conditions, failure to thrive and oxygen dependent. Cystic fibrosis was excluded by negative sweat tests and CFTR mutations study. CT scan confirmed diffuse interstitial lung disease and “honeycombing” appearance. Pulmonary biopsy showed an interstitial lung disease with lamellar bodies anomalies typical of surfactant proteins deficiency.  The genetic mutations analysis showed a new mutation in the exon 3 of the gene encoding SP-C.Patients with severe respiratory failure and/or interstitial lung disease should be always investigated for surfactant protein deficiency, particularly if other more common diseases are excluded.
DLL4 promotes continuous adult intestinal lacteal regeneration and dietary fat transport
Authors: Jeremiah Bernier-Latmani, Christophe Cisarovsky, Cansaran Saygili Demir, Marine Bruand, Muriel Jaquet, Suzel Davanture, Simone Ragusa, Stefanie Siegert, Olivier Dormond, Rui Benedito, Freddy Radtke, Sanjiv A. Luther, Tatiana V. Petrova
Journal: Journal of Clinical Investigation (2015)

The small intestine is a dynamic and complex organ that is characterized by constant epithelium turnover and crosstalk among various cell types and the microbiota. Lymphatic capillaries of the small intestine, called lacteals, play key roles in dietary fat absorption and the gut immune response; however, little is known about the molecular regulation of lacteal function. Here, we performed a high-resolution analysis of the small intestinal stroma and determined that lacteals reside in a permanent regenerative, proliferative state that is distinct from embryonic lymphangiogenesis or quiescent lymphatic vessels observed in other tissues. We further demonstrated that this continuous regeneration process is mediated by Notch signaling and that the expression of the Notch ligand delta-like 4 (DLL4) in lacteals requires activation of VEGFR3 and VEGFR2. Moreover, genetic inactivation of Dll4 in lymphatic endothelial cells led to lacteal regression and impaired dietary fat uptake. We propose that such a slow lymphatic regeneration mode is necessary to match a unique need of intestinal lymphatic vessels for both continuous maintenance, due to the constant exposure to dietary fat and mechanical strain, and efficient uptake of fat and immune cells. Our work reveals how lymphatic vessel responses are shaped by tissue specialization and uncover a role for continuous DLL4 signaling in the function of adult lymphatic vasculature.
Knee pain and the infrapatellar branch of the saphenous nerve
Authors: T D Tennent, N C Birch, M J Holmes, R Birch, N J Goddard
Journal: Journal of the Royal Society of Medicine (1998)

Pain over the front of the knee is common after surgery or trauma but often a definite diagnosis is difficult to make. Over the past year we have seen five cases in which the pain could be ascribed to damage to a branch of the infrapatellar branch of the saphenous nerve. Two were subsequent to trauma and three to surgical procedures. In all five cases surgical exploration gave symptomatic relief. Eight cadaveric knees were prosected to explore further the anatomy of this nerve in relation to the injuries. Injury to one of these branches should be considered in cases of persistent anterior, anteromedial or anterolateral knee pain or neurological symptoms following surgery or trauma.
MABEL—A large multinational study of cetuximab plus irinotecan in irinotecan resistant metastatic colorectal cancer
Authors: H. Wilke, R. Glynne-Jones, J. Thaler, A. Adenis, P. Preusser, E. Aranda Aguilar, M. Aapro, N. Van Den Berg, S. Eggleton, S. Siena
Journal: Journal of Clinical Oncology (2006)

3549 Background: Cetuximab is an IgG1 anti-EGFR monoclonal antibody, active alone and in combination with irinotecan in metastatic colorectal cancer (mCRC) patients (pts) who failed irinotecan (Cunningham et al, NEJM 2004). MABEL investigated cetuximab plus irinotecan in an uncontrolled, multicenter study in pts with EGFR-detectable mCRC whose last treatment regimen contained irinotecan. MABEL is to date the largest cetuximab study published in this setting. Methods: Primary endpoint was the progression-free survival (PFS) rate at 12 weeks (wks), (expected rate 50% ± 3%). Study treatment was cetuximab, initial dose 400 mg/m 2 , weekly 250 mg/m 2 , plus irinotecan with dose and schedule as pre-study: Regimen A: 125 mg/m 2 weekly for 4/6 wks, B: 180 mg/m 2 q 2 wks, or C: 350 mg/m 2 q 3 wks. Results: 197 centers from 7 countries screened tumors of 1681 pts for EGFR expression: 1461 (87%) pts had EGFR-detectable tumors. 1123 pts are currently evaluable: median age is 62 years (25–84), Karnofsky status ≥70% in all pts, and 64% pts were male. 64% pts had ≥ 2 prior therapy lines. 76% pts were also pretreated with oxaliplatin. On-study distribution of pts to irinotecan regimens was A: 92, B: 674, C: 357. 12-week PFS rates were: A: 60% (50–71%); B: 60% (56–64%); C: 63% (58–68%); overall: 61% (58–64%), and at 24 wks: A: 29% (19–39%); B: 32% (28–36%); C: 39% (34–45%); overall 34% (31–37%). The current estimate of median survival, based on 717 deaths, is 9.2 (8.7–9.9) months. Treatment was generally well tolerated with grade 3/4 adverse events &gt;5%: diarrhea 20%, skin and subcutaneous tissue disorders incl. acne-like rash 19%, neutropenia 9%, asthenia 8%. Grade 3/4 immune system disorders incl. hypersensitivity reactions occurred in 1.5%, hypomagnesemia in 0.4% pts. Conclusions: The PFS rates observed in this heavily pretreated population fully met the primary endpoint of this study. Similar PFS rates were seen at 12 weeks (overall 61%) and 24 weeks (overall 34%) for all irinotecan regimens. Estimated survival time is in line with previously published results. MABEL clearly confirmed in a wider setting the efficacy and safety of cetuximab plus irinotecan seen in previous studies. [Table: see text]
Endometrial Carcinoma in BD II/Han Rats: Model of a Spontaneous Hormone-Dependent Tumor
Authors: F Deerberg, J Kaspareit
Journal: JNCI Journal of the National Cancer Institute (1987)

The incidence of endometrial carcinomas as well as the life-spans of 5 groups of female BD II/Han inbred rats were compared. Groups compared were control (CON), ovariectomized (OV), retired breeder (RB), germfree rats (GF), and rats fed a purified diet (PD). Carcinomas, for the most part adenocarcinomas, occurred in 90% of the CON and PD rats and approximately 60% of the RB and GF rats. Carcinomas did not develop in OV rats. The mean life-span of the CON and PD rats was 22 months. The RB and GF rats reached, respectively, 32 and 30 months; and the OV rats, 39 months. An essential influence of ovarian hormones on tumorigenesis was shown. Alimentary carcinogens and phytoestrogens, as well as chronic irritations of the endometrium due to bacteriologic inflammations, could be excluded as tumor initiators. Hormonal dysregulation in the aging BD II/Han rats was discussed as a possible cause of an inappropriate stimulation of the endometrium, promoting a previously transformed tumor cell or initiating an autonomous tumor growth. Such evidence supports the use of the BD II/Han rat as a suitable model for the study of hormonal effects on the tumorigenesis of endometrial carcinomas in women.