tbuckley/cabot-search huggingface dataset:
Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion–Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations
Authors: Yen-Fu Chen, Min-Shu Hsieh, Shang-Gin Wu, Yih-Leong Chang, Chong-Jen Yu, James Chih-Hsin Yang, Pan-Chyr Yang, Jin-Yuan Shih
Journal: Journal of Thoracic Oncology (2016)

IntroductionThe efficacy of pemetrexed-based chemotherapy in patients with advanced lung adenocarcinoma with novel ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) oncogenic rearrangement is unclear. This study aimed to compare the efficacy of pemetrexed-based chemotherapy in patients with advanced ROS1-fusion lung adenocarcinoma with its efficacy in those having different driver mutations.MethodsWe retrospectively identified patients with advanced lung adenocarcinoma who were screened for epidermal growth factor receptor gene (EGFR) mutations, echinoderm microtubule associated protein like 4 gene (EML4)–anaplastic lymphoma receptor tyrosine kinase gene (ALK) translocation, Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutations, and ROS1 fusion by using multiplex reverse-transcriptase polymerase chain reaction. Patients who received pemetrexed-based therapy were enrolled for further analysis. The demographic data, clinical outcomes, and thymidylate synthase immunostaining (H-score) of patients with ROS1 fusion–positive lung adenocarcinomas were compared with those of patients harboring EGFR mutations, EML4-ALK fusion, KRAS mutations, and quadruple negativity.ResultsA total of 253 patients with advanced lung adenocarcinoma received a pemetrexed-based regimen and were classified on the basis of molecular findings as follows: 102 patients (40.3%) with EGFR mutations, 32 patients (12.6%) with EML4-ALK translocation, three patients (1.2%) with KRAS mutations, 19 patients (7.5%) with ROS1 fusion, and 97 patients (38.3%) with quadruple-negative status. Patients with ROS1 fusion had a better overall response rate (57.9%, p = 0.026), disease control rate (89.5%, p = 0.033), and longer progression-free survival (7.5 months, p = 0.003) compared with patients harboring other driver mutations. However, the H-score of thymidylate synthase was not associated with the response to pemetrexed therapy in patients with different molecular subtypes of lung adenocarcinoma.ConclusionsROS1 fusion positivity is probably a favorable factor of pemetrexed-based therapy for patients with lung adenocarcinoma.
RARE-17NEUROENDOCRINE CARCINOMA IN THE BRAIN
Authors: Masaki Okada, Takahiro Kanda, Daisuke Ogawa, Aya Shinomiya, Tetsuhiro Hatakeyama, Keisuke Miyake, Takashi Tamiya
Journal: Neuro-Oncology (2015)

OBJECT: Neuroendocrine carcinoma (NEC) is a malignant tumor that usually arises in the lung, pancreas and gastrointestinal tract. Brain metastasis of NEC is merely reported. Herein, we report two cases of NEC in the brain mimicking glioblastoma (GBM). CASES: Both patients were in their 60s, cystic lesions with peritumoral edema affected the temporal lobe. Cyst walls were thin but hyperintense in diffusion weighted images implying increased cellularity. Positron emission tomography (PET) revealed malignant nature by strong uptake of methionine (MET), fluorothymidine (FLT) and fluoromisonidazole likewise GBM. However, fluorodeoxyglucose (FDG) indicated relatively weak uptakes compared as GBM. Both tumors were resected under the preoperative diagnosis of GBM, however, pathological diagnoses were NEC by immunohistochemical finding of negative GFAP and positive markers of neuroendocrine differentiation. Systemic examination failed to reveal the origin. Both cases underwent radiotherapy. One case was lost by spinal dissemination 11 months after the operation. DISCUSSION: FDG-PET of neuroendocrine tumor in the extracranial lesion does not always demonstrate strong uptake. FDG-PET for NEC in the brain could be less accumulated than GBM, while it should be evaluated keeping in mind that the background level of FDG would be high in the brain tissue. In case of malignant tumors endorsed by other tracer such as MET and FLT, inconsistent FDG-PET finding might be useful for the diagnosis of NEC in the brain.
Case 24-2012
Authors: Amir T. Fathi, Yi-Bin Chen, Brett W. Carter, Russell J.H. Ryan
Journal: New England Journal of Medicine (2012)

A 38-year-old man had weakness, abdominal pain, and confusion; he also had anemia, thrombocytopenia, hypercalcemia, circulating abnormal T cells, generalized lymphadenopathy, and hepatosplenomegaly. A diagnostic procedure was performed.
Treatment of Endometriosis and Other Gynecologic Conditions with Large Doses of Estrogens
Authors: Lewis M. Hurxthal, Anne T. Smith
Journal: New England Journal of Medicine (1952)

THE use of stilbestrol in the treatment of endometriosis was described in 1948 by Karnaky1 and Hurxthal and Arnold.2 The purpose of this report is to relate further experience with the use of this drug in the treatment of endometriosis and in a few other conditions.In their original communication, Hurxthal and Arnold2 described 3 cases in which stilbestrol was tolerated with favorable results. The first patient in whom endometriosis was verified remains well and is amenorrheic after treatment for five years. Nodules cannot be palpated on pelvic examination. On several occasions, the drug has been discontinued, and painful menstruation . . .
Case 17-1968
Authors: Martin J. Wohl, Benjamin Castleman
Journal: New England Journal of Medicine (1968)

Presentation of CaseA sixty-three-year-old man was admitted to the hospital because of pain in the back.Three months previously there was the onset of diarrhea and insomnia, and he became nervous and irritable. He complained of weakness in the legs and intolerance of heat; almost continuous sweating occurred. During the three months before admission his appetite was good, although he lost 6 pounds in weight, and he experienced diffuse pain in the lower portion of the back, pelvis and thighs and at times throughout the body. A week before entry nausea and increasing weakness developed, and he lost his . . .
Abstract 246: Translocation Of Myomirs Via Gap Junction Channels Prevents Cancer Cell Growth
Authors: Laura Graciotti, Toru Hosoda, Marcello Rota, Giulia Borghetti, Sergio Signore, Piero Anversa, Annarosa Leri
Journal: Circulation Research (2014)

The adult heart is resistant to cancer formation and the metastatic invasion of distant neoplasms. This biological advantage may be dictated by the molecular properties of myocytes that constitutes 90% of the myocardium. We raised the possibility that microRNAs (miRs) highly expressed in myocytes (myomirs) may translocate via gap junctions to neighboring cancer cells, preventing their growth or inhibiting their survival. First, we established whether overexpression of myomirs interferes with the proliferation and death of MCF7 human breast cancer cells. Infection of MCF7 with lentiviruses carrying miR-1, miR-133a and miR-499 (miR-MCF7) resulted in a 5-fold decrease in Ki67 labeling and a 20% increase in the fraction of cells arrested at G0/G1. In contrast, TdT-positive apoptotic cells averaged 0.5% and did not differ in miR-MCF7 and control cells. To mimic the in vivo condition, EGFP-labeled MCF7 were co-cultured with myocytes and, 4 days later, the expression of myomirs was measured in FACS-sorted MCF7. With respect to baseline, co-cultured MCF7 showed 100-fold, 16-fold, and 27-fold increase in the expression of miR-1, miR-133a and miR-499, respectively. Co-culture of myocytes and MCF7 led to the formation of gap junctions made of connexin 43 (Cx43) and connexin 45 (Cx45). Silencing of Cx43 and Cx45 decreased significantly the expression of myomirs in co-cultured MCF7. Importantly, proximity of MCF7 to myocytes reduced markedly the growth rate of the cancer cells. Subsequently, 1 x 106 MCF7 or miR-MCF7 were injected subcutaneously in NOD-scid mice. At 5 weeks, the tumors developed from miR-MCF7 were 70% smaller than those originated from control MCF7. Two doses of breast cancer cells were injected intramyocardially to establish their in situ tumorigenic effects. Tumor formation was found in all hearts that received 1 x 106 MCF7. Conversely, mice injected with 1 x 105 cells did not show macroscopic evidence of neoplastic lesions. The lack of tumor development in the latter case is consistent with the ability of the heart to prevent neoplasm development when cancer cell colonization is not massive. Our findings document that miR-1, miR-133a and miR-499 translocate from myocytes to cancer cells via gap junctions, inhibiting tumor growth in vitro and in vivo.
Notice of Retraction and Replacement. Hollon et al. Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial.<i>JAMA Psychiatry</i>. 2014;71(10):1157-1164
Authors: Steven D. Hollon, Robert J. DeRubeis, Jan Fawcett, Jay D. Amsterdam, Richard C. Shelton, John Zajecka, Paula R. Young, Robert Gallop
Journal: JAMA Psychiatry (2016)

Notice of Retraction and Replacement. Hollon et al. Effect of cognitive therapy with antidepressant medications vs antidepressants alone on the rate of recovery in major depressive disorder: a randomized clinical trial. JAMA Psychiatry. 2014;71(10):1157-1164
&lt;italic&gt;N&lt;/italic&gt;-Nitroso-&lt;italic&gt;N&lt;/italic&gt;-methylurea-Induced Mammary Carcinogenesis: Effect of Pregnancy on Preneoplastic Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: C J Grubbs, D L Hill, K C McDonough, J C Peckham
Journal: JNCI Journal of the National Cancer Institute (1983)

The effect of pregnancy and lactation on mammary cancers induced with N-nitroso-N-methylurea (NMU) was determined in female outbred Sprague-Dawley rats. The animals received 5 mg NMU/100 g body weight at 50 days of age and were divided into the following groups: virgin, pregnancy (beginning 10 days after NMU administration), pregnancy and lactation (beginning 10 days after NMU), and pregnancy and lactation (beginning 82 days after NMU). The time of appearance of the first palpable cancers was shorter in rats undergoing an early pregnancy. Few cancers, however, were detected from rats after pregnancy or pregnancy and lactation was completed, and a decrease in cancer incidence from virgin rats was observed in these animals at termination of the study. Since NMU is a direct-acting carcinogen with a short half-life, no effect of pregnancy on carcinogen metabolism or binding could have occurred. Preneoplastic cells present before pregnancy appeared to have been either altered (such that their latent period was increased) or destroyed by the hormones associated with pregnancy.
Distinctive Genotypes In Infants With T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Authors: Marcela B Mansur, Frederik W Van Delft, Caroline L Furness, Mariana Emerenciano, Susan M Colman, Emma Butcher, Helena Kempski, Emmanuelle Clappier, Hélène Cave, Jean Soulier, Maria S. Pombo-de-Oliveira, Mel Greaves, Anthony M Ford
Journal: Blood (2013)
Increased Insulin Concentrations in Nondiabetic Offspring of Diabetic Parents
Authors: Steven M. Haffner, Michael P. Stern, Helen P. Hazuda, Braxton D. Mitchell, Judith K. Patterson
Journal: New England Journal of Medicine (1988)

Insulin resistance is thought by many to be the primary defect that results in non-insulin-dependent diabetes mellitus (NIDDM). An implication of this theory is that prediabetic persons have higher serum insulin levels than normal subjects. We assessed serum insulin concentrations in a cohort of 1497 nondiabetic Mexican Americans, a population at high risk for NIDDM, according to whether their parents or siblings had diabetes. It was assumed that prediabetic persons would be more likely to have strong family histories of diabetes. We found a stepwise increase in fasting insulin levels in nondiabetics with neither, one, or both parents with diabetes (69.8, 77.8, and 94.6 pmol per liter, respectively; P = 0.002). Similar results were observed for insulin sum (the total of insulin concentrations in the fasting state and at 30, 60, and 120 minutes after a 75-g oral glucose load). The differences in insulin sums according to family history remained statistically significant in analyses of covariance, which controlled for variations in body-mass index, body-fat distribution, and level of blood glucose. Subjects without diabetes who had a diabetic sibling had higher fasting concentrations of insulin than subjects without a diabetic sibling (83.2 vs. 69.6 pmol per liter), but the difference was not statistically significant. We conclude that prediabetic persons, who would be expected to be more numerous in kindreds with progressively stronger family histories of diabetes, have hyperinsulinemia. This supports the insulin-resistance hypothesis.
Deficiency of Lysosomal Acid Phosphatase
Authors: Henry L. Nadler, Thomas J. Egan
Journal: New England Journal of Medicine (1970)

Acid phosphatase activity in a patient with a new familial metabolic disorder (characterized by intermittent vomiting, hypotonia, lethargy, opisthotonos, terminal bleeding and death in early infancy) was deficient in the lysosomal fraction of homogenates of cultivated fibroblasts, brain, liver, spleen and kidney. Amniotic-fluid cells obtained at 13 weeks in a subsequent pregnancy had no demonstrable acid phosphatase activity. The pregnancy was interrupted, and no detectable levels of acid phosphatase were found in homogenates of fetal organs. The lysosomal fraction of homogenates of cultivated fibroblasts from both parents (first cousins) had acid phosphatase levels of 3.0 ± 0.9 μmoles of p-nitrophenol phosphate (PNP) per hour per microgram of protein as compared to control levels of 7.2 ± 0.7 μmoles of PNP. Heterozygotes could not be distinguished from controls in untreated lymphocytes, whereas marked differences were found after 56 hours of phytohemagglutinin treatment. This suggests that the condition is inherited as an autosomal recessive disorder.
Tricyclic antidepressant sample stability and the vacutainer effect
Authors: M Zetin, H R Rubin, R Rydzewski
Journal: American Journal of Psychiatry (1981)

The authors studied the effects of different sample handling techniques on 17 tricyclic plasma samples. They found that the samples were stable at room temperature for up to 3 days when kept in a glass tube sealed with Parafilm, but the samples were not stable when stored in a Vacutainer tube with the stopper in contact with the plasma.
Favorable outcome in excessive methotrexate (MTX) intoxication after high-dose (HD) MTX therapy by early use of carboxypeptidase G2 (CPG2)
Authors: S. Schwartz, K. Müller, L. Fischer, A. Korfel, K. Jahnke, T. Auton, E. Thiel
Journal: Journal of Clinical Oncology (2005)

8255 Background: Renal failure with accumulation of MTX after HD-MTX therapy is a potentially devastating complication. CPG2 cleaves MTX into non-toxic metabolites, whereas in this situation hemodialysis is ineffective. Little is known on the clinical efficacy of CPG2 in pts. with renal failure and excessive MTX accumulation. Methods: In a nationwide survey, we have evaluated pts. treated with CPG2 for very severe MTX-intoxication and renal failure. Results: Four pts. (age: 20–35 years; 2 male, 2 female; 2 osteosarcoma, 2 chondrosarcoma) with renal failure and a serum MTX (sMTX) level >100μmol/l at registration were identified. HD-MTX-therapy (5464 to 12005mg/m2) was given as a 4 hour infusion. Pts. were registered at 19, 40, 48 and 48 hours after start of HD-MTX when sMTX-levels were 567, 304, 158 and 292μmol/l, respectively. Serum creatinin levels at registration ranged from 308–362μmol/l. Risk factors contributing to renal failure were overweight (BMI >=25kg/m2; n=2), suboptimal hydration (n=2), low urine pH (n=2), preexisting renal insufficiency (n=2), comedication interfering with renal MTX-excretion (n=2) and urine flow obstruction (n=1). CPG2 (15–35units/kg/body weight) was given as a single intravenous injection 28–61hours after start of HD-MTX. In all pts., CPG2 was tolerated without side effects. Serum creatinin levels peaked (331–508μmol/l) days 0–5 and returned to normal in all pts. by days 23–43 after CPG2 treatment. Extrarenal grade III/IV MTX-toxicity were mucositis (n=1), liver (n=3), central nervous (n=2) and hematological toxicity (n=2). Conclusions: CPG2 is an effective, well tolerated antidote in patients with excessive MTX-intoxication and facilitates complete recovery from renal failure in these high-risk pts. More studies are needed to evaluate more precisely the efficacy of an early use of CPG2 and its potential role as a standard rescue agent. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Protherics PLC Protherics PLC Protherics PLC Protherics PLC
Brief Communication: Unexpected High Incidence of Primary Liver Cancer in Geneva, Switzerland
Authors: A. J. Tuyns, M. Obradovic
Journal: JNCI Journal of the National Cancer Institute (1975)

The age-standardized incidence rate of primary liver cancer (PLC) in Geneva was 9.7 per 100,000 in males, a figure four or five times higher than incidence rates reported elsewhere in Europe . These PLC's were often associated with cirrhosis and alcoholism. This indicated that the toll of PLC related to alcoholism and to alcoholic cirrhosis may be greater than anticipated.
Serum Metabolomic Analysis Identifies Potential Biomarkers for Aspirin-Exacerbated Respiratory Disease
Authors: Ga Young Ban, Kumsun Cho, Seung-Hyun Kim, Moon Kyoung Yoon, Chang Gyu Jung, Ji-Ho Lee, Sohee Lee, Ji Hye Kim, Shin Yoo Seob, Ye Young-Min, Dong-Ho Nahm, Joo-Youn Cho, Hae-Sim Park
Journal: Journal of Allergy and Clinical Immunology (2016)
Continuous Glucose Monitoring in Patients With Type 1 Diabetes Using Insulin Injections
Authors: Nicole C. Foster, Kellee M. Miller, William V. Tamborlane, Richard M. Bergenstal, Roy W. Beck
Journal: Diabetes Care (2016)

Continuous glucose monitoring (CGM) has been demonstrated in randomized trials to improve glucose control in patients with type 1 diabetes (T1D) (1–3); however, most of the participants in these trials have used a pump for insulin delivery, and the use of CGM in T1D patients receiving insulin by injection has not been well studied.

We used the T1D Exchange registry database to assess the impact of CGM on HbA1c in insulin injection users. Details on the informed consent process, eligibility criteria, and data collection methods have been previously published (4). Participants were defined as CGM users if CGM was used for real-time diabetes management during the 30 days prior to the clinic visit.

Among the 17,731 registry participants with T1D duration >1 year who had a clinic visit between June 2014 and October 2015, 6,222 (35%) used injections alone, 8,783 (50%) used pump alone, 2,316 (13%) used pump with CGM, and 410 (2%) used injections with CGM. A Dexcom CGM was being used by …
Perspectives in Oncology Drug Pricing
Authors: James P. Stevenson, Matt Kalaycio, Brian Bolwell
Journal: JAMA Oncology (2016)

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Abstract P2-12-07: Treatment of the breast in occult breast cancer: Results of a prospective Dutch national cohort study with 5 years follow up
Authors: M de Maat, R Bretveld, J Steevens, Y Vissers, K Hulsewé
Journal: Cancer Research (2016)

Abstract Introduction Occult breast cancer (cT0N+M0) is a rare diagnosis and there is insufficient evidence on which to base treatment of the ipsilateral breast. Methods From 2006 till 2008 the Dutch National Cancer Registry identified patients nationwide with possible occult breast cancer. These patients were diagnosed with axillary nodal metastases with no evidence of the primary tumor on physical examination, mammography and ultrasound. Data on histopathology, imaging diagnostics and treatment were collected. After a minimum of 5 years follow up, data on recurrence and survival were gathered and analyzed. Results A group of 71 patients with occult breast cancer was identified. Of these, 7 patients received no local therapy. The remaining 64 patients all underwent surgery with axillary lymph node dissection. Ninety-two percent had MRI of the breast. Three groups were formed: Group A (n=25) had surgery of the breast, group B (n=28) received breast irradiation and group C (n=11) consisted of patients who had no treatment of the breast. Recurrence in the ipsilateral breast was seen in 4 patients (14%) in group B and in 3 patients (30%) in group C. There was 1 local recurrence in group A after breast conserving treatment and no significant differences between groups. After a median of 85 months of follow-up, overall survival (72%, 82% and 82% for group A, B and C, respectively) and distant recurrence rates (12%, 11% and 10% for group A, B and C, respectively) were not significantly different between groups assessed by log-rank test. Conclusion In occult cT0N+M0 breast cancer, conservative treatment of the breast is an acceptable modality which results in similar distant recurrence and overall survival rates. Surgery and breast irradiation appear to reduce the risk of ipsilateral breast recurrence. This is the first prospective study that provides evidence in the current clinical setting to guide treatment for patients with occult breast cancer. Citation Format: de Maat M, Bretveld R, Steevens J, Vissers Y, Hulsewé K. Treatment of the breast in occult breast cancer: Results of a prospective Dutch national cohort study with 5 years follow up. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-12-07.
Pseudocyesis
Authors: D. O'Neill
Journal: BMJ (1955)

A Case of PseudocyesisA woman of 41 complained of "peculiar feelings" in the abdomen, pain in the breasts, and morning sickness.She had not menstruated for eight months.The abdomen " felt tight," and she said it was much larger than usual.Two successive pregnancy tests were negative, and she was shown the results; her comment was: " I question the tests.They may be wrong.I think it's an eight-months pregnancy."The sensations in her abdomen, were described as " like a mouse."She had married in 1947, and was most eager to have a child.No contraceptives were employed, yet she did not