tbuckley/cabot-search huggingface dataset:
Association of FcγRIIa and FcγRIIa polymorphisms with clinical outcome in metastatic colorectal cancer patients (mCRC) treated with cetuximab and irinotecan
Authors: F. Bibeau, E. Crapez, F. Di Fiore, S. Thezenas, J. Sabourin, A. Lamy, T. Frebourg, P. Michel, M. Ychou, F. Boissiere-Michot
Journal: Journal of Clinical Oncology (2008)

11004 Background: Cetuximab, a chimeric monoclonal IgG1 targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated clinical efficacy in mCRC patients refractory to Irinotecan, mainly in wild type KRAS tumors. Besides the inhibition of the EGFR pathway, Cetuximab may exert anti-tumor effects through antibody-dependent cell-mediated cytotoxicity (ADCC). This phenomenon is an important anticancer mechanism in which antibody Fc portion interacts with Fc receptors (FcγRs) expressed by immune effector cells. ADCC is influenced by two FcγRs (FcγRIIa and FcγRIIIa), whose polymorphisms (FcγRIIa-H131R and FcγRIIIa- V158F) could affect their affinity for IgG1. We wondered whether these two polymorphisms could impact the clinical outcome of mCRC patients treated with Cetuximab and Irinotecan. Methods: We examined FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms and KRAS tumor mutational status in 69 mCRC patients by direct sequencing, multiplex allele-specific PCR and SnaPshot assay, respectively. DNA from normal and tumor tissues was extracted from paraffin-embedded samples. All patients were initially refractory to Irinotecan and received Cetuximab associated with Irinotecan. Clinical response was evaluated using RECIST criteria (Complete Response, Partial Response (PR), Stable or Progressive Disease). Results: KRAS mutations were significantly associated with the absence of response (1 PR among 27 mutated patients vs 10 PR among 37 wild type patients, p=0.021; Fisher's exact test). Patients with HH and/or VV homozygous genotypes have a longer median progression free survival (PFS) than those carrying R and F alleles (5.5 vs 3 months, p=0.005; log-rank test). In KRAS mutated patients, HH and/or VV homozygous genotypes were also associated with a longer PFS than those with R and F alleles (3.2 vs 2.8 months, p=0.015). Conclusions: Our study shows that FcγRIIa131 HH and/or FcγRIIIa158 VV genotypes have a favorable impact on the clinical outcome of mCRC patients treated with Cetuximab and Irinotecan. Moreover, these polymorphisms are clinically relevant in KRAS mutated patients, suggesting the important role of ADCC in Cetuximab efficacy. No significant financial relationships to disclose.
WHO calls for efforts to prevent newborn deaths in South East Asia
Authors: Cheryl Travasso
Journal: BMJ (2016)

The World Health Organization and others, including Unicef, the World Bank, and UNAIDS, have pledged their support to help countries in South East Asia to gain access to lifesaving interventions to reduce newborn mortality. A technical advisory group of 12 regional and global experts has been set up.

Some 894 000 newborns (<28 days old) died in the region in 2015, amounting to 7400 deaths a day. Of these, 696 000 newborn deaths were in India, which recorded the highest neonatal mortality rate (28 deaths per 1000 live …
Abstract 19337: Cathepsin L is Required to Modulate Cardiac Hypertrophy through Activation of the Autophagy-Lysosomal Dependent Protein Processing Pathway
Authors: Mark Moon, Mei Sun, Maral Ouzounian, Guohua Li, Youan Liu, Anthony Gramolini, Peter P Liu
Journal: Circulation (2012)

Background_Autophagy is critical in the maintenance of cellular protein quality control involved in the cell growth, survival and death. Cathepsin L (CTSL) is a key member of the lysosomal protease family that is expressed in the murine and human heart, and may play an important role in dynamic protein control. We hypothesized that CTSL is important in regulating protein processing in the heart, particularly under pathological stress. Methods and Results_Phenylephrine-induced cardiac hypertrophy in vitro was significantly more pronounced in CTSL deficient neonatal cardiomyocytes compared to controls. This was accompanied by a significantly increased accumulation of autophagosomes, increased levels of ubiquitin-conjugated protein, impaired protein degradation and increased cell death. These phenomena were rescued with Ctsl1 replacement via adeno-associated virus mediated gene transfer. In the in vivo murine model of aortic banding (AB), CTSL deficiency (Ctsl-/-) markedly exacerbated cardiac hypertrophy, worsened cardiac function, and increased mortality. Ctsl-/- AB mice demonstrated significantly decreased lysosomal activity, and increased sarcomere-associated protein aggregation. Homeostasis of the endoplasmic reticulum was also altered with increased Bip and GRP94 proteins in Ctsl-/- AB mice, accompanied by increased ubiquitin-proteasome system activity and higher levels of ubiquitinated proteins in response to AB. These changes ultimately led to a decrease in cellular ATP production, enhanced oxidative stress, and increased cellular apoptosis. Conclusions_Lysosomal CTSL is a key contributor to modulate the cardiac response to hypertrophic stress through regulation of protein processing and quality control.
Renal Hypertension: Review
Authors: W G GUNTHEROTH, C L HOWRY, J S ANSELL
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Phase II study of fenretinide in patients with small cell lung cancer (SCLC) with progression after first- or second-line chemotherapy
Authors: B. J. Schneider, F. Worden, S. Gadgeel, C. Hodges, R. Parchment, J. Zwiebel, M. Kraut, G. Kalemkerian
Journal: Journal of Clinical Oncology (2004)

7299 Background: Alterations in retinoid signaling appear to be involved in the pathogenesis of SCLC. Fenretinide [N-(4-hydroxyphenyl) retinamide], a synthetic retinoid, inhibits the growth of SCLC cells in vitrovia the induction of apoptosis. We evaluated the clinical activity of fenretinide in relapsed/refractory SCLC. Methods: Inclusion criteria included progressive SCLC after 1 or 2 chemotherapy regimens and PS 0–2. Patients with stable, treated CNS metastases were eligible. Fenretinide 900 mg/m2 PO BID was administered on days 1–7 of each 21-day cycle. Blood and sputum were collected pre-treatment and on day 7 of cycle 1 to measure drug levels by HPLC. Results: 19 patients were enrolled: median age 63 yrs (43–80); gender 9M:10F; prior chemotherapy regimens 1 in 15 pts, 2 in 4 pts; median time from diagnosis to enrollment 10 months (7–40). The median number of cycles of fenretinide was 2 (1–17). Six of 18 evaluable patients (30%) had stable disease (SD) after 2–17 cycles. Eleven patients had progressive disease after 1 or 2 cycles, 2 of whom had progression of symptoms despite radiographic SD. The median time to treatment failure was 5.1 wk (1–19) in all patients and 13 wk in patients with SD. Median survival was 25 wk (6–125), with 3 patients alive at 40–70 wks. Toxicity included mild, reversible visual changes (haziness, altered night vision), grade 1–3 nausea/vomiting, and grade 1 diarrhea. One patient developed pancreatitis on day 2 of cycle 1 due to metastatic pancreatic duct obstruction. The average day 7 plasma fenretinide level was 3103 ± 1707 ng/ml (7.9 ± 4.4 μM; n=14). Average pre-treatment and day 7 serum retinol levels were 471 ± 159 ng/ml and 51 ± 71 ng/ml, respectively. Conclusions: Fenretinide is well tolerated in patients with SCLC. Concentrations of fenretinide that induce cytotoxicity in vitro are clinically achievable. Stabilization of disease has been noted in 30% of patients with this aggressive disease. No significant financial relationships to disclose.
Randomized phase 3 trial of irinotecan (CPT-11) + 5FU/folinic acid (FA) vs CDDP + 5FU in 1<sup>st</sup>-line advanced gastric cancer patients
Authors: M. Dank, J. Zaluski, C. Barone, V. Valvere, C. Peschel, M. Wenczl, E. Goker, M.-L. Risse, L. Awad, R. Bugat
Journal: Journal of Clinical Oncology (2005)

4003
Long term complications from treatment in survivors of high risk neuroblastoma
Authors: C. Laverdiere, N. K. V. Cheung, B. H. Kushner, K. Kramer, S. Modak, M. P. La Quaglia, S. Wolden, K. K. Ness, J. G. Gurney, C. A. Sklar
Journal: Journal of Clinical Oncology (2004)

8543 Background: Few studies have assessed late effects in neuroblastoma (NB) survivors. Methods: 63 high risk NB patients were seen at the Long Term Follow-Up Clinic since 1991. Results: Median age at diagnosis was 3.0 years. 11 patients had stage 3 disease and 52 stage 4 (2 stage 2B initially). Median follow-up was 7.06 years. All patients had surgery and received chemotherapy, 56 (89%) radiation therapy, 38 (60%) immunotherapy and 35 (56%) autologous stem cell transplant. 60 patients (95%) had late effects and 18 (29%) had more than three. The most frequent complications were: hearing loss (62%), primary hypothyroidism (24%), ovarian failure (41% of females), musculoskeletal (21%), pulmonary (19%), neurocognitive (14%), visual (14%), dental (13%) and secondary neoplasms (6%). Grades of severity were: 1 (24%), 2 (44%), 3 (28%) and 4 (4%) (CTCAE v 3.0). Survivors who received cisplatinum were more at risk to develop hearing loss compared to those who did not receive it ( OR, 9.74; 95% CI: 0.9–101.6). A total cyclophosphamide dose greater than 7.4 g was associated with ovarian failure (p=0.02). Pulmonary dysfunction was correlated with chest irradiation (p=0.009). Visual and dental problems were both associated with cranial radiation (p=0.001 and p=0.002 respectively). In a subset of 28 patients who were prepubertal at their first visit, there was a significant correlation between the change in height SDS (−0.28) and the follow-up time (p=0.04). Conclusions: Despite very intensive multimodality treatment, survivors of high-risk NB face relatively moderate late effects. Their early identification and treatment are important for the quality of life of the survivors. No significant financial relationships to disclose.
Reply to G.J. Weiss
Authors: Karyn B. Stitzenberg, YunKyung Chang
Journal: Journal of Clinical Oncology (2015)

Weiss 1 brings up an interesting question with regard to the influence of the evolution of operative technique on patterns of readmission and total costs of care for complex cancer procedures.Increasingly, these procedures are being performed, either partially or entirely, in a minimally invasive fashion, either thoracoscopically/ laparoscopically or robotically.In our initial study of patterns of readmission, 2 we did not examine surgical approach.As a result, we returned to our data to attempt to address Weiss's inquiry.Our study captured incident cases of bladder, esophagus, lung, and pancreas cancer from 2001 to 2007, for which extirpative surgery was performed before the end of 2008.During this time period, we were unable to identify any patients who had both an extirpative procedure and a robotic procedure coded for the same encounter.This may in part be a result of the fact that uptake of robotic approaches for these complex procedures is a recent trend, and it is likely that only a few robot-assisted surgeries were performed before 2009.However, this question also highlights one of the challenges and limitations that is encountered when using administrative claims data for research.When examining the entire cohort of 216,470 patients who were diagnosed with bladder, esophageal, lung, and pancreas cancer from 2001 to 2007, regardless of whether they met inclusion criteria for our study, we identified only 61 patients who had any procedure of any type performed robotically.All 61 of those procedures occurred during or after October 2008.Delving deeper, we found that the International Classification of Diseases (9th revision, clinical modification) codes for robotic surgery were only first intro-duced in 2008 (codes 17.4 and 17.49) and 2009 (codes 17.41-17.45).Any robotic procedures performed before 2008 would likely have been coded as laparoscopic procedures, or possibly even as open procedures.Even after the codes were introduced, experience tells us that, in general, there is usually a learning curve lag between the introduction of new codes and complete uptake by medical coders.As a result, although codes became available in 2008, robotic procedures were likely underreported in administrative claims during 2008 and 2009.In the end, we cannot answer the important question posed by Weiss 1 using the data from our study, 2 but we completely agree that outcomes such as readmissions, use of postacute services, and global costs of care need to be considered when fully evaluating the risks/ benefits of new surgical approaches such as robot-assisted surgery.
Patient Preferences for Adjuvant Interferon Alfa-2b Treatment
Authors: Kerry L. Kilbridge, Jane C. Weeks, Arthur J. Sober, Frank G. Haluska, Craig L. Slingluff, Michael B. Atkins, Dana E. Sock, John M. Kirkwood, Robert F. Nease
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Although trials of adjuvant interferon alfa-2b (IFNα-2b) in high-risk melanoma patients suggest improvement in disease-free survival, it is unclear whether treatment offers improvement in overall survival. Widespread use of adjuvant IFNα-2b has been tempered by its significant toxicity. To quantify the trade-offs between IFNα-2b toxicity and survival, we assessed patient utilities for health states associated with IFN therapy. Utilities are measures of preference for a particular health state on a scale of 0 (death) to 1 (perfect health). PATIENTS AND METHODS: We assessed utilities for health states associated with adjuvant IFN among 107 low-risk melanoma patients using the standard gamble technique. Health states described four IFNα-2b toxicity scenarios and the following three posttreatment outcomes: disease-free health and melanoma recurrence (with or without IFNα-2b) leading to cancer death. We also asked patients the improvement in 5-year disease-free survival they would require to tolerate IFN. RESULTS: Utilities for melanoma recurrence with or without IFNα-2b were significantly lower than utilities for all IFNα-2b toxicities but were not significantly different from each other. At least half of the patients were willing to tolerate mild-moderate and severe IFNα-2b toxicity for 4% and 10% improvements, respectively, in 5-year disease-free survival. CONCLUSION: On average, patients rate quality of life with melanoma recurrence much lower than even severe IFNα-2b toxicity. These results suggest that recurrence-free survival is highly valued by patients. The utilities measured in our study can be applied directly to quality-of-life determinations in clinical trials of adjuvant IFNα-2b to measure the net benefit of therapy.
Amelioration of Runt Disease in Rats by Metopirone
Authors: Tohru Abe, M.D., Masuko Nomura
Journal: JNCI Journal of the National Cancer Institute (1970)

Runt disease in rats was ameliorated by Metopirone. To induce runt disease, 4-week-old SWF1 hybrid rats (♂Sprague-Dawley × ♀ Wistar) were given an intraperitoneal injection of a suspension of spleen cells. Runt disease appeared in 173 of 240 recipients (72.1%). After onset of the disease, some rats were left untreated, while others received 25 mg Metopirone via gastric tube daily for 5 days. On the 10th day after onset of the disease, survival in the untreated group was 69.8% (44/63), while in the treated group it was 82.0% (50/61). On the 20th day, survival in the untreated group was 8.9% (4/45), while in the treated group it was 67.9% (36/53). Amelioration of runt disease in rats by Metopirone is associated with an increase in the total number of lymphocytes, which results from the increased ratio of lymphocytes to granulocytes in the circulating blood. The results show that the process of runt disease, induced by injection of parental spleen cells into rats, can be reversed—at least within 5–7 days after regular weight loss—by the increase in the number of circulating blood lymphocytes which compensate for the lymphopenia caused by runt disease.
Cutaneous genital complications of antiangiogenic agents
Authors: C. Mateus, C. Massard, G. Tomasic, J. Wechsler, V. Boige, A. Le Cesne, J. C. Soria, B. Escudier, C. Robert
Journal: Journal of Clinical Oncology (2009)

e14568 Background: Multikinase inhibitors targeting VEGFR, i.e. sorafenib and sunitinib are associated with various cutaneous side effects (1). Five cases of scrotal skin lesions were recently reported in male patients treated with sunitinib (2). Our observations of 8 patients presenting with genital inflammatory lesions during various anti-VEGFR therapies show that this side effect is linked to VEGFR blockade and not specifically to sunitinib and that it can also occur in women. Results: Six men and two women were seen for a genital eruption. They were treated with sorafenib (3 pts), sunitinib (5 pts), and a new pan-HER and VEGFR inhibitor (BMS 514, EVRI) (1 pt) for renal cell cancer (4 pts), hepatocellular carcinoma (2 pts), lung cancer (1 pt) and sarcoma (1 pt). Genital lesions occurred during the first six weeks of treatment. They appeared as a painful erythematous and squamous inguinal, intergluteal, and perianal rash rapidly involving all genital areas in 4 patients. Lesions became erosive in 3 cases. Four men presented more limited, pruriginous and lichenoid penile papules which were associated with a genital erythema for 3 of them. In one patient, penile inflammation resulted in a phimosis. One patient successively treated with sunitinib, sorafenib and once again with sunitinib experienced genital side effects with both agents. Patients taking sequential sunitinib treatment reported symptoms improvement during treatment interruptions and recurrences during the weeks on therapy. Microbiological samples were negative. Pathology of erythematous and squamous lesions showed a psoriasiform or a lichenoid aspect. Topical steroids were efficient for 5 patients but 3 patients had to interrupt anti-VEGF therapy because of their genital rash. Conclusions: Polymorphous genital inflammatory rash is a new skin side effect that can be associated with any cancer therapies targeting VEGFR in men and in women. Its frequency is unknown and probably underestimated because many patients might not report this side effect and its mechanism is still obscure. Physicians should be aware of this side effect and should inquire as to whether the patients have noticed such symptoms in order to avoid worsening thereof by symptomatic measures. No significant financial relationships to disclose.
Abstract 18079: Female Gender Associated with Increased Disability in Ischemic Strokes Secondary to Atrial Fibrillation
Authors: Ryan C Martin, Aarti Patel, Adam Rafi, Wasef Michael, Kerolos Fahmi, Matthew B Schabath, Bonnie Kirby, Sanders H Chae, David Z Rose, Michael G Fradley, William S Burgin, Arthur J Labovitz
Journal: Circulation (2014)

Background:  In the latest AHA/ACC atrial fibrillation (AF) guidelines, CHA 2 DS 2 -VASc replaced the CHADS 2  assessment of stroke risk to determine prophylactic anticoagulation. This change reflects studies demonstrating increased risk of stroke in women with AF compared to men. However, the literature has not examined if this relation also applies to stroke severity. In our retrospective review of 186 consecutive patients who presented with ischemic stroke due to AF, we examined the hypothesis that women are not only at higher risk for ischemic stroke, but also at higher risk of a disabling stroke.   Methods:  We explored the patients’ clinical features, including demographics, admission labs, echo results, and CHA2DS2-VASc / CHADS 2  risk scores. To assess stroke severity we reviewed each patient’s modified Rankin Scale (mRS) at discharge as well as NIH stroke scale at admission and discharge. We focused on those with a fatal stroke (mRS of 6) or disabling stroke (mRS 4-5), defined as need for max assistance with ambulation or activities of daily living.   Results:  Females made up 60% of the patient population examined. As expected, women had a significantly higher risk of stroke than men on review of CHA 2 DS 2 -VASc scores (4.95 ± 0.5 vs 3.78 ± 0.62, p  2  scores were similar (2.76 ± 0.31 female vs 2.66 ± 0.46 male, p=0.1), suggesting that the increased risk is secondary to the variables unique to CHA 2 DS 2 -VASc. Review of mRS revealed a similar rate of fatal stroke (24.7% female vs 24.6% male, p= 0.98). Amongst survivors, women had a significantly higher risk of a disabling stroke (63.5% vs 47.2%, p= 0.05).   Conclusion:  Multiple studies of AF and stroke have previously demonstrated that women are at higher risk to suffer ischemic strokes than men. This is supported by the larger female population in our series. However, to our knowledge this is the first study of a large series of patients with ischemic stroke secondary to AF to demonstrate the increased risk of disabling strokes amongst women with AF. This data suggests the importance of early awareness and initiation of anticoagulation for AF in the female population and indicates the need for further study into the effect of anticoagulation on the prevalence of disabling stroke in the AF population.