tbuckley/cabot-search huggingface dataset:
Combination Chemotherapy of L1210 Leukemia With Platinum Compounds and Cyclophosphamide Plus Other Selected Antineoplastic Agents 2
Authors: Glen R. Gale, Loretta M. Atkins, Sandra J. Meischen, Alayne B. Smith, Ernest M. Walker
Journal: JNCI Journal of the National Cancer Institute (1976)

Six antitumor platinum compounds were used in combination with cyclophosphamide plus 1 of 7 other antitumor drugs for treatment of L1210 leukemia in B6D2F1 [(C57BL/6 × DBA/2) F1] mice. Data obtained from each three-agent regimen were compared with those obtained after administration of each compound alone and each appropriate two-agent combination. No cure (>60-day survival) was obtained with any compound used alone. Combination of cyclophosphamide with a platinum compound (Pt+CY) yielded a collective cure rate of 193/420, and the addition of a third drug to the Pt+CY combination increased by 50% the collective cure rate to 290/420 (P<0.001). Certain regimens produced 100% cure rates. The most effective drugs when used in combination with PT+CY were cytosine arabinoside, 5-fluorouracil, hydroxyurea, and Yoshi-864. Adriamycin, methotrexate, and vincristine were less effective at the doses used. Toxicity, as evidenced by maximum weight loss, was slightly greater with the three-agent combinations than with the Pt+CY regimens
Renal Tubular Acidosis
Authors: R. Curtis Morris
Journal: New England Journal of Medicine (1981)

Several kinds of tubular dysfunction can underlie renal tubular acidosis (RTA), a syndrome of disordered renal acidification that causes metabolic acidosis without (or with only a moderate) reduction in renal mass. Slowly developing and painfully disabling osteomalacia was once the major metabolic consequence of untreated RTA of the physiologic type first investigated in detail1 — now termed Type 1 or "classic" RTA (RTA-1) — and characterized by an inappropriately high urinary pH during severe as well as mild acidosis.2 But nowadays in the United States, the hyperchloremic acidosis that characterizes all physiologic subtypes of RTA is so readily detected, and . . .
Clinical Use of the Insulin Infusion Pump in 100 Patients with Type I Diabetes
Authors: Robert S. Mecklenburg, James W. Benson, Nancy M. Becker, Patricia L. Brazel, Paul N. Fredlund, Robert J. Metz, Robert L. Nielsen, Carolyn A. Sannar, William J. Steenrod
Journal: New England Journal of Medicine (1982)

We investigated the efficacy of insulin-pump therapy in insulin-dependent diabetics, aged 18 to 69 years, by comparing the metabolic control achieved in 100 patients using this technique with that previously obtained by conventional insulin therapy. Patients were followed during pump therapy for as long as 15 months. Fasting and nonfasting blood glucose levels (mean +/- S.E.M.) decreased from 201 +/- 6 and 213 +/- 6 mg per deciliter (11.2 +/- 0.3 and 11.8 +/- 0.3 mmol per liter), respectively, to 158 +/- 5 and 145 +/- 3 mg per deciliter (8.77 +/- 0.3 and 8.05 +/- 0.2 mmol per liter) after one month of pump therapy (P less than 0.001). Ninety-three patients had improved blood sugar control; 71 per cent had a mean blood sugar concentration of 150 mg per deciliter (8.3 mmol per liter) or less after six months. Glycosylated hemoglobin values became normal in 44 per cent of 88 patients who had follow-up determinations. In over 500 patient-months there were four episodes of ketoacidosis and five episodes of serious hypoglycemia. Three patients abandoned pump therapy. We conclude that insulin-pump therapy is acceptable to patients and that it can be successfully applied to clinical practice and large-scale research studies.
Sleep reduction as a final common pathway in the genesis of mania [published erratum appears in Am J Psychiatry 1987 Apr;144(4):542]
Authors: T A Wehr, D A Sack, N E Rosenthal
Journal: American Journal of Psychiatry (1987)

Diverse psychological, interpersonal, environmental, and pharmacological factors that appear to trigger the onset of mania could act via their capacity to cause sleep deprivation, a mechanism that has been shown in experiments with bipolar patients to induce transient or sustained switches into mania. Since mania in turn causes insomnia, the development of mania is potentially self-reinforcing and could become autonomous after being initiated by precipitating factors. The sleep reduction model is based on experimental evidence and is a parsimonious explanation for the precipitation of manic episodes by a wide variety of factors. Furthermore, this model has clear implications for the prevention and treatment of mania and provides a conceptual focus and an experimental paradigm for psychological investigations of the causes of mania.
Case 26-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Richard Masters, Stanley J. Robboy
Journal: New England Journal of Medicine (1973)

Presentation of CaseAn 11-year-old girl was admitted to the hospital because of fever and a rash.She was well until 15 months previously, when anorexia occurred, with a daily rise of the temperature as high as 39.4°C, a generalized erythematous rash and a weight loss of 5 kg. Two months later arthralgias developed, with swelling of the fingers and ankles, a fleeting erythematous macular rash over much of the body and uveitis. She was seen at this hospital, where tests for rheumatoid factor and antinuclear antibody and an L.E.-cell test were negative. A diagnosis of juvenile rheumatoid arthritis was . . .
A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced gastric cancer.
Authors: H. Ohnuma, Y. Sato, T. Takayama, T. Sagawa, M. Hirakawa, K. Harada, T. Nobuoka, K. Hirata, Y. Sato, Y. Takahashi, S. Katsuki, S. Takahashi, M. Hirayama, M. Takahashi, M. Maeda, T. Sato, K. Miyanishi, M. Kobune, R. Takimoto, J. Kato
Journal: Journal of Clinical Oncology (2011)

4057 Background: We have previously reported that phase II studies of combination chemotherapy with docetaxel, cisplatin and S-1 (DCS) demonstrated a very high response rate (87.1%) and a promising survival time (MST 687 days) in patients with unresectable advanced gastric cancer (BJC 2008, CCP 2009). This regimen showed no case of PD and an appreciable rate of downstaging, suggesting the applicability of DCS to neoadjuvant chemotherapy (NAC). We therefore conducted a multicenter phase II trial to evaluate the efficacy and safety of neoadjuvant DCS for locally advanced gastric cancer. Methods: The study included patients (pts) with histologic confirmation of gastric cancer, no prior chemotherapy, adequate organ function, PS 0-1, age 20-80, and clinical stages of cT3-4, cN0-3, and cM0 (Japanese staging system). S-1 80 mg/m2 was administered orally on days 1-14, followed by intravenous administration of cisplatin 60 mg/m2on day 8, and docetaxel 60 mg/m2on day 8. All pts received 2 courses of treatment every 3 weeks and responders received a maximum of 4 courses, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability and the secondary endpoints included response rate, histological response, survival time, and safety. Results: From July 2006 to November 2010, 40 pts (median age 66, male/female 28/12, PS0/1 29/11) were enrolled. The median number of courses received was 2 (1-4). Response rate was 71.8% with 29 PR and 11 SD cases. Grade 3/4 adverse events were leukopenia (55.0%), neutropenia (55.0%), febrile neutropenia (17.5%), diarrhea (22.5%), anorexia (25.0%), and nausea (17.5%), but they were generally transient and manageable. Curative surgery was performed in 39 pts; 36 pts (92.3%) underwent R0 resection. Downstaging was achieved in 26 pts and pathological response was found in 24 pts. There were no treatment-related deaths and no major surgical complications. Conclusions: Neoadjuvant DCS chemotherapy demonstrated a high response rate and a sufficient R0 resection rate for locally advanced gastric cancer with manageable toxicities. The results suggested the efficacy of DCS regimen in the neoadjuvant setting.
Severe recalcitrant cutaneous manifestations in systemic lupus erythematosus successfully treated with fumaric acid esters
Authors: A.M. Saracino, C.H. Orteu
Journal: British Journal of Dermatology (2016)

Fumaric acid esters (FAEs) have proven efficacy in the treatment of psoriasis and have been in use for decades. More recently, as their mechanism of action and abundant immunomodulatory effects become clearer, the potential benefits of treating other inflammatory skin conditions using FAEs are increasingly being recognized. The use of FAEs as combination systemic therapy has not been well studied and data are lacking regarding the safety and efficacy of this type of therapy. In this case report, three patients with severe, extensive and recalcitrant cutaneous manifestations of systemic lupus erythematosus (SLE) (one case of disseminated discoid lesions and two with severe chilblain lesions) were treated with Fumaderm® (containing the FAE dimethylfumarate and monoethylhydrogen fumarate salts), after failing to respond to a multitude of other monotherapies and combination therapies. All patients showed a substantial clinical response when FAEs were added to their treatment, with concurrent improvements in quality‐of‐life instrument scores. The treatment was well tolerated in the context of systemic organ involvement and as combination therapy with other agents, such as hydroxychloroquine and mycophenolate mofetil. These cases of SLE illustrate the potential use of FAEs in severe, disfiguring and otherwise therapy‐resistant skin lesions, including, to our knowledge, the first two reported cases of FAE‐treated chilblain lupus erythematosus.
Psychological Issues in Geriatric Oncology
Authors: Archna Sarwal, Andrew J. Roth
Journal: Journal of the National Comprehensive Cancer Network (2003)

Optimism about improved survival from cancer has increased. However, even with tremendous improvements in screening techniques and treatment, a cancer diagnosis may shatter the dream of a dignified old age for elderly patients. Cancer diagnosis and treatment often produce psychological stresses resulting from the actual symptoms of the disease, as well as the patient and family's perceptions of the disease and its stigma. Concerns related to cancer have particular meaning for aging individuals who undergo these situations in the context of retirement, widowhood, other medical disabilities, and other losses. Today, patients and families are more interested in treatment issues and quality of life, both during and after treatment. In this article we discuss late life depression, anxiety, and delirium and treatments related to elderly patients coping with cancer.
Congenital Anomalies in Children of Patients Who Received Chemotherapy for Cancer in Childhood and Adolescence
Authors: Daniel M. Green, Michael A. Zevon, Geoffrey Lowrie, Nina Seigelstein, Brenda Hall
Journal: New England Journal of Medicine (1991)

Many patients who have been treated successfully for childhood cancer with regimens that contain one or more mutagenic chemotherapeutic agents are concerned that their own treatment during childhood or adolescence may adversely affect their children.
Early Administration of Vapreotide for Variceal Bleeding in Patients with Cirrhosis
Authors: P Calès, C Masliah, B Bernard, P P Garnier, C Silvain, N Szostak-Talbodec, J P Bronowicki, D Ribard, D Botta-Fridlund, P Hillon, K Besseghir, D Lebrec
Journal: New England Journal of Medicine (2001)

In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown.
Seminoma (Germinoma) Apparently Primary in the Anterior Mediastinum
Authors: Lewis B. Woolner, Robert W. Jamplis, John W. Kirklin
Journal: New England Journal of Medicine (1955)

TERATOID tumors originating in the anterior mediastinum are well known. In our experience they constitute the commonest tumor at this site. The majority are cystic and benign.1 Morphologically, various derivatives of the three germ layers are encountered in these benign tumors, including neural tissue, skin and appendages, teeth, bone, cartilage, muscle, endothelial tissue, respiratory epithelium and pancreas.Malignant teratomas make up a relatively small group of primary anterior mediastinal tumors. Microscopically, they exhibit fewer well differentiated structures than benign tumors do. The malignant component, as in malignant teratomas elsewhere, is usually adenocarcinoma (teratocarcinoma). These two groups of tumors are commonly . . .
Genetic and Clinical Features of Hemoglobin H Disease in Chinese Patients
Authors: Frederick E. Chen, Clara Ooi, Sau Yin Ha, Bernard M.Y. Cheung, David Todd, Raymond Liang, Tai Kwong Chan, Vivian Chan
Journal: New England Journal of Medicine (2000)

Normally, one pair of each of the two α-globin genes, α1 and α2, resides on each copy of chromosome 16. In hemoglobin H disease, three of these four α-globin genes are affected by a deletion, a mutation, or both. We studied the α-globin gene abnormalities and the clinical and hematologic features of Chinese patients with hemoglobin H disease in Hong Kong.
The histone deacetylase inhibitor trichostatin A suppresses murine innate allergic inflammation by blocking group 2 innate lymphoid cell (ILC2) activation
Authors: Shinji Toki, Kasia Goleniewska, Sara Reiss, Weisong Zhou, Dawn C Newcomb, Melissa H Bloodworth, Matthew T Stier, Kelli L Boyd, Vasiliy V Polosukhin, Sriram Subramaniam, R Stokes Peebles
Journal: Thorax (2016)

Group 2 innate lymphoid cells (ILC2) are an important source of the type 2 cytokines interleukin (IL)-5 and IL-13 that are critical to the allergic airway phenotype. Previous studies reported that histone deacetylase (HDAC) inhibition by trichostatin A (TSA) downregulated adaptive allergic immune responses; however, the effect of HDAC inhibition on the early innate allergic immune response is unknown. Therefore, we investigated the effect of TSA on innate airway inflammation mediated by ILC2 activation.BALB/c mice were challenged intranasally with Alternaria extract, exogenous recombinant mouse IL-33 (rmIL-33) or the respective vehicles for four consecutive days following TSA or vehicle treatment. Bronchoalveolar lavage (BAL) fluids and lungs were harvested 24 h after the last challenge.We found that TSA treatment significantly decreased the number of ILC2 expressing IL-5 and IL-13 in the lungs challenged with Alternaria extract or rmIL-33 compared with vehicle treatment (p<0.05). TSA treatment significantly decreased protein expression of IL-5, IL-13, CCL11 and CCL24 in the lung homogenates from Alternaria extract-challenged mice or rmIL-33-challenged mice compared with vehicle treatment (p<0.05). Further, TSA treatment significantly decreased the number of perivascular eosinophils and mucus production in the large airways that are critical components of the asthma phenotype (p<0.05). TSA did not change early IL-33 release in the BAL fluids; however, TSA decreased lung IL-33 expression from epithelial cells 24 h after last Alternaria extract challenge compared with vehicle treatment (p<0.05).These results reveal that TSA reduces allergen-induced ILC2 activation and the early innate immune responses to an inhaled protease-containing aeroallergen.
Targeting Na<sup>+</sup>/K<sup>+</sup>-ATPase in non-small cell lung cancer (NSCLC)
Authors: B. Nilsson, T. Mijatovic, A. Mathieu, I. Roland, E. Van Quaquebeke, F. Van Vynckt, F. Darro, R. Kiss
Journal: Journal of Clinical Oncology (2007)

18144 Background: Non-small cell lung cancer patients that present with grade IIIB or stage IV disease have a median survival of 5–7 months if left untreated. With modern chemotherapy overall survival may be 11–12 months, but still no patients are cured. We have investigated the impact of modulation of the a-1 subunit of Na + /K + -ATPase in NSCLC. Methods: Cancer tissue from 59 patients with NSCLC (30 adenocarcinomas and 29 squamous cell cancers) and 25 normal lung samples as well as four human NSCLC cell lines (A549, Cal-12T, NCI-H727, A427) were assessed with regard to expression of the a-1 subunit of Na + /K + -ATPase (sodium pump) by use of immunohistochemistry. In addition, A549 cells were transfected with specific a-1 siRNA for study of a-1 subunit expression and of cell proliferation and migration. Protein expression was analyzed by Western blotting. Cell proliferation was assessed by MTT and cell migration by video microscopy. Cell lines were exposed to varying concentrations of ouabain, digoxin, digitoxin and UNBS1450, a novel cardenolide targeting the a-1 subunit of Na + /K + -ATPase for study of proliferation, migration, and inhibition of the target. Results: Expression of the a-1 subunit of Na + /K + - ATPase was elevated in almost half of the tissue samples from patients with NSCLC compared to normal controls. The a-1 subunit was also overexpressed in A549, Cal-12T and NCI-H727 cells. Transfection of A549 cells with siRNA resulted in markedly decreased expression of the a- 1 subunit and also to reduced migration and proliferation of such cells. UNBS1450 at 10 and 100 nM for 72 hours reduced A549 cell migration and proliferation similar to that observed with anti- a-1 siRNA. Digoxin had no activity at these concentrations. Conclusions: Inhibition of the a-1 subunit of Na + /K + -ATPase is associated with significant decrease of cell migration and proliferation and has potential as a therapeutic strategy in NSCLC. No significant financial relationships to disclose.
Abstract 4429: EGR1-MIR152pathway overcomes acquired cisplatin resistance in ovarian cancer cells by inhibiting cyto-protective autophagy via ATG14
Authors: Jun He, Jing-Jie Yu, Bing-Hua Jiang
Journal: Cancer Research (2015)

Abstract The cytotoxic-based platinum compound cisplatin has been commonly used in ovarian cancer treatment for almost three decades. However, the intrinsic and acquired resistance to cisplatin in cancer cells remains a big challenge for overall survival. A growing body of evidence indicates a role of autophagy as a prosurvival and resistance mechanism against chemotherapy. Here, we reported MIR152 as a new autophagy-regulating miRNA that plays a role in cisplatin resistance. We showed that MIR152 expression was dramatically downregulated in the cisplatin-resistant cell lines A2780/CP70, SKOV3/DDP compared with their respective parental cells, and in ovarian cancer tissues associated with cisplatin resistance. Overexpression of MIR152 sensitized cisplatin-resistant ovarian cancer cells by reducing cisplatin-induced autophagy, enhancing cisplatin-induced apoptosis and inhibition of cell proliferation. A mouse subcutaneous xenograft tumor model using A2780/CP70 cells with overexpressing MIR152 was established and displayed decreased tumor growth in response to cisplatin. We also identified that ATG14 is a functional target of MIR152 in regulating autophagy inhibition. Furthermore, we found that EGR1 (early growth response 1) regulated the MIR152 gene at the transcriptional level. Ectopic expression of EGR1 enhanced efficacy of chemotherapy in A2780/CP70 cells. More importantly, these findings were relevant to clinical cases. Both EGR1 and MIR152 expression levels were significantly lower in human ovarian cancer tissues with high levels of ERCC1 (excision repair cross-complementation group 1), a marker for cisplatin resistance. Collectively, these data provide insights into novel mechanisms for acquired cisplatin resistance. Activation of EGR1 and MIR152 may be a useful therapeutic strategy to overcome cisplatin resistance by preventing cyto-protective autophagy in ovarian cancer. Note: This abstract was not presented at the meeting. Citation Format: Jun He, Jing-Jie Yu, Bing-Hua Jiang. EGR1-MIR152 pathway overcomes acquired cisplatin resistance in ovarian cancer cells by inhibiting cyto-protective autophagy via ATG14. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4429. doi:10.1158/1538-7445.AM2015-4429
Cloning of Human Hematopoietic Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Imamura, Tatsuo, Huang, Chester C., Minowada, Jun, Takahashi, Morinobu, Moore, George E.
Journal: JNCI Journal of the National Cancer Institute (1970)

The cloning characteristics of 28 human hematopoietic cell lines, 10 derived from normal persons, 12 from patients with malignant diseases, and 6 from patients with nonmalignant diseases, have been studied in a soft agar medium. All cell lines derived from the buffy coat of normal individuals and those from patients without hematopoietic malignancies had cloning efficiencies of less than 6% and developed no macroscopic colonies. Of 12 lines derived from patients with leukemia or myeloma, 4 showed intermediate cloning efficiencies of 12–36% and some macroscopic colonies, whereas the remainder had characteristics of normalcy and probably were derived from normal elements in the blood. A cell line from a patient with multiple myeloma had a cloning efficiency of more than 60%. Generally, intermediate and high cloning efficiencies were correlated with abnormal chromosome constitutions. With one exception (cell line RPMI 5157 from a patient with acute lymphocytic leukemia), low cloning efficiencies and an absence of macroscopic colonies characterized cell lines with a normal diploid chromosome pattern. Correlation between cloning efficiency and the presence or absence of the herpes-type virus (leukovirus) was not observed. Lines with high and intermediate cloning efficiencies could be subcultured from much smaller cell inocula than could lines with low cloning efficiencies; i.e., they were less dependent on population density in culture. Cloned sublines were similar to parental cell lines with respect to cloning efficiency, chromosome constitution, and production of immuneglobulins. Cloning efficiency of human hematopoietic cell lines may be regarded as an indirect indicator of the relative normality or malignancy of the cells.
Parathyroid Hormone Secretion in Familial Vitamin-D-Resistant Rickets
Authors: Richard E. Reitz, Richard L. Weinstein
Journal: New England Journal of Medicine (1973)

Parathyroid function was determined in four adults and one child with familial vitamin-D-resistant rickets. All subjects demonstrated hypophosphatemia, whereas the total serum calcium and magnesium showed no consistent pattern as compared to normal subjects. Peripheral parathyroid hormone concentrations were elevated in all subjects. Hypocalcemia induced by sodium ethylenediaminetetra-acetic acid in three adults produced a greater increase in parathyroid hormone secretion than in normal subjects. The increased concentrations of parathyroid hormone, both basal and during induced hypocalcemia, are consistent with Albright's hypothesis that the hyperparathyroidism in these subjects is due to decreased absorption of calcium from the gastrointestinal tract. (N Engl J Med 289:941–945, 1973)
Intravenous Urography in Multiple Myeloma
Authors: Cecil Morgan, William J. Hammack
Journal: New England Journal of Medicine (1966)

ACUTE renal failure in patients with multiple myeloma who have had intravenous urography has had increased emphasis over the last few years.1 2 3 4 5 A direct cause- and-effect relation between the acute renal failure and intravenous urography seems to be accepted by many clinicians. Leucutia,6 on the basis of 5 cases in the Scandinavian and American medical literature, has stated that intravenous urography should not be performed for any reason in patients known to have multiple myeloma. Other authors have agreed by indicating, in clinical research protocols, that the patients with myeloma were not to be subjected to intravenous urography.7 The present . . .