tbuckley/cabot-search huggingface dataset:
Cancer burden in women with hereditary non-polyposis colorectal cancer (HNPCC)
Authors: M. Harris
Journal: Journal of Clinical Oncology (2005)

9624 Background: Lifetime cancer burden is significant for men and women with HNPCC. In addition to cancers of “other sites” women with HNPCC are estimated to have a 40–60% lifetime risk of developing uterine cancer and an up to 10% lifetime risk of developing ovarian cancer. Methods: Cancer diagnoses of Australian (Victorian) women with HNPCC were reviewed to determine the frequency of cancer and the frequency of gynaecological compared to “other” cancer diagnoses. Female mutation carriers were identified from Familial Cancer Centre database records. From pedigrees first degree female relatives of mutation positive females who had been diagnosed with HNPCC related cancers, and female obligate HNPCC mutation carriers were also identified. Verified cancer diagnoses of these women were recorded. Results: 107 women from 50 families were included. Twenty-four women (22%) belonged to families with an MLH1 mutation, 79 (74%) to families with an MSH2 mutation and 4 (4%) had MSH6 mutations. Twenty-three women (21%) were unaffected by cancer at a median age of 37 years (range 20–88 years). Only five of these were over 40 years of age. Of the women diagnosed with cancer (N=84 or 79%), 50/84 (60%) had colorectal cancer with a median age at first diagnosis of 39 years (range 29–80 years); 32/84 (38%) had CRC only. Thirty-six of 84 (43%) had a gynaecological cancer; 29/84 (35%) had endometrial cancer diagnosed at a median age of 51 (range 39–71 years) and 5/84 (6%) had ovarian cancer (all diagnosed < 50 years of age).Twenty of 84 women with cancer (23%) had a gynaecological cancer alone (15 endometrial, 5 ovarian). Fifteen of 84 women (18%) had both CRC and uterine cancer. Twelve of 107 women (11%) had had prophylactic hysterectomy and oophorectomy. Of 84 women diagnosed with cancer 23 (27%) had more than one cancer and 11 (13%) had 3 or more. Of those with cancer 10 (12%) had breast cancer, 5 (6%) had stomach cancer, 3 (4%) had small bowel cancer, 3 (4%) had transitional cell carcinomas of the urinary tract, 4 (5%) had Muir Torre syndrome and 1 (1%) had a primary brain tumour. Conclusions: Cancer burden in women with HNPCC is significant due to the combination of gynaecological cancers, as well as CRC and cancers of “other” sites; however CRC remains the commonest primary cancer site. No significant financial relationships to disclose.
Abstract 15053: Prevalence and Clustering of Cardiovascular Risk Factors Across the National Income Spectrum in the Africa Middle East Region
Authors: Alawi A Alsheikh-Ali, Mohamed I Omar, Frederick J Raal, Wafa Rashed, Omar Hamoui, Abdoul Kane, Mohamed Alami, Paula Abreu, Walid M Mashhoud
Journal: Circulation (2014)

Background:  Developing countries account for a large proportion of global deaths from cardiovascular disease (CVD). Macroeconomic factors may exacerbate the burden of CVD in these countries. We evaluated CVD risk factor (CVDRF) prevalence in the Africa and Middle East (AfME) region according to national income categories.   Methods:  The Africa Middle East Cardiovascular Epidemiological (ACE) Study is a multinational cross-sectional study evaluating the prevalence of CVDRFs (hypertension, diabetes mellitus, dyslipidemia, obesity, smoking and abdominal obesity) in stable adult outpatients attending 94 general practice clinics across 14 countries in the AfME region. Countries were classified using World Bank definitions into low-income (LI), lower-middle income (LMI), upper-middle income (UMI), and high-income (HI) groups.   Results:  In total, 4,378 patients were recruited [age 46 ±14 years, 52% female, 260 (6%) from LI countries, 1,324 (30%) from LMI countries, 1,509 (35%) from UMI countries, and 1,285 (29%) from HI countries]. Dyslipidemia was the most prevalent risk factor, reported in > 2/3rd of the population across the 4 national income categories. The prevalence of diabetes, obesity (BMI ≥ 30 kg/m2) and smoking increased with higher national incomes reaching 32%, 44%, and 16%, respectively in HI countries. Abdominal obesity was reported in at least ~ 2/3rd of the cohort across national income levels. CVDRFs tended to cluster with half (53%) of the overall cohort having ≥ 3 CVDRFs. CVDRF clustering (≥ 3 CVDRFs) was more prevalent with higher national income, ranging from 33% in LI countries to 57% in HI countries.   Conclusions:  CVDRFs are widely prevalent across the national income spectrum in the AfME region. Higher income countries have a larger burden of diabetes, obesity and smoking, and a higher prevalence of CVDRF clustering. Economic development should be coupled with aggressive public health measures to limit the associated increase in CVDRF burden.
Is the difference in reexcision rate of various margin assessment methods due solely to difference in volume excised?
Authors: C. K. Culpepper, J. I. Goldberg, L. Choi, E. Brogi, L. Sclafani, T. A. King, A. S. Heerdt, A. S. Reiner, S. Patil, K. J. Van Zee
Journal: Journal of Clinical Oncology (2010)

593 Background: The inability to achieve clear margins in a single operation continues to plague breast surgeons, resulting in reexcision rates of up to 70%. We explored 3 different methods of margin assessment (METHODs) and found that the cavity shave technique (C) resulted in significantly lower reexcision rates, but larger volumes of excision. Here, we assessed whether the lower reexcision rate was due solely to the larger volume excised. Methods: Our study population consisted of consecutive patients undergoing breast conservation with sentinel node biopsy after a needle biopsy diagnosis of invasive carcinoma or DCIS from July-December of 2003, 2004, and 2008. These 3 time periods corresponded to 3 METHODs: perpendicular (P) (pathologist evaluated perpendicular margins in serial sections of the specimen, 2003), tangential shaved (T) (pathologist shaved margins from the specimen, 2004), and cavity shaved (C) (surgeon shaved margins from the cavity, 2008). Volume of tissue excised at initial excision was the sum of the volume of lumpectomy (calculated by πABC/6, where A, B, C are 3 dimensions of specimen) and additional margins taken (calculated by πABH/4, where A, B are diameters, H is thickness). Using univariate and multivariate logistic regression, we modeled the outcome of >1 excision versus 1 excision with METHOD and ln(volume) as predictors. Results: See Table. On univariate logistic regression, both METHOD (OR 1.7 for T vs. C, p=0.03) and volume (OR=0.8 for ln[volume], p=0.02) were statistically significantly associated with need for reexcision. When adjusted for volume, METHOD remained significant (OR 1.6 for T vs. C, p=0.02). Conclusions: Our study showed that while C is associated with a larger volume of excision, the lower reexcision rate seen is not due solely to the larger volumes excised. These data suggest that other factors resulting in reexcision, such as artifactual ink at or near tumor, are less likely with C technique due to the separate margins resected. Hazard ratios with 95% confidence intervals Perpendicular (P) Tangential shave (T) Cavity shave (C) P value Number of breasts 174 160 299 Reexcision rate 28% 35% 24% 0.05* Mean volume 63 cm3 70 cm3 78 cm3 0.003† * Chi-squared test. † ANOVA model using ln(volume). No significant financial relationships to disclose.
Rotavirus Vaccine and Severe Diarrhea in African Infants
Authors: Chengfeng Xu, Dahai Hu, Wanfu Zhang
Journal: New England Journal of Medicine (2010)

This author reply letter discusses three topics that highlight the successful results and major implications of the study for the development of a rotavirus vaccine and its clinical evaluation in developing countries. It touches on: the concept of the natural molecular evolution of rotavirus strains the potential heterotypic cross-protection offered by the monovalent G1P[8] rotavirus vaccine against strains with neither G1 nor P[8] specificity and the concept of potential interference in vaccine efficacy from antibodies in breast milk.
Abstract 5260: Mitochondrial DNA phylogenetic analysis for local recurrences and second primary tumors from patients with oral cavity squamous cell carcinoma
Authors: Chih-Hsiung Lai
Journal: Cancer Research (2015)

Abstract Local recurrences (LRs) and second primary tumors (SPTs) are commonly observed in patients with oral squamous cell carcinoma (OSCC). A lower survival rate has been demonstrated in patients with LRs with respect to patients with SPTs. Therefore, the criteria for differentiating LRs and SPTs are indispensable for determining appropriate treatment. Currently, criteria based on histology, the distance and relapse time between new lesions and index primary tumor are generally used in clinical classification. In the genomic era, molecular classification based on the clonal relationship between the first and the second lesions may be more reliable than traditional clinical classification. The aim of the present study tried to establish a feasible molecular classification based on mitochondrial DNA (mtDNA) phylogenetic analysis. The study population consisted of 44 OSCC patients with multiple lesions for a total of 47 (19 LRs and 28 SPTs) paired lesions. The mtDNA analysis was performed by direct sequencing. The phylogenetic and molecular evolutionary analyses were conducted by using MEGA software version 6 and three common phylogenetic evolutionary methods (Maximun Likelihood (ML), Neighbor-Joining (NJ) and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) method) were applied. Preliminary analysis indicated that the prevalence of clonality for LRs and SPTs was 26.3% and 3.6%, respectively. A discrepancy between the clinical classification and mtDNA analysis was found in 15 paired tumors (31.9%) in which 14 paired lesions were classified as LRs based on clinical criteria, while mtDNA analysis suggested that they were nonclonal-related SPTs. Survival analysis indicated that there was no difference between patients with LRs and patients with SPTs based on clinical classification. On the other hand, patients with clonal second lesions had poorer overall survival than patients with nonclonal second lesions based on mtDNA analysis. In conclusion, our preliminary findings suggested that molecular clonality analysis could improve the accuracy in differentiating LRs from SPTs. Citation Format: Chih-Hsiung Lai. Mitochondrial DNA phylogenetic analysis for local recurrences and second primary tumors from patients with oral cavity squamous cell carcinoma. [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 5260. doi:10.1158/1538-7445.AM2015-5260
Vitamin A and childhood mortality [letter]
Authors: Grabowsky M
Journal: New England Journal of Medicine (1991)

The possible reasons for the ineffectiveness of small weekly doses of vitamin A in preventing death from measles in a study in the Trichy district of Tamil Nadu India are suggested in this letter to the editor.  There was only a statistically insignificant 54% reduction in deaths from measles in contrast to deaths from other causes in the study and also contrasted with dramatic results in other published reports.  There are several reasons why the children in this study may have not been at risk of death from measles.  It is known that 50% of children in this area are immune at 36 months; that 8.9% of the children in the study population are under 1 year and therefore protected by maternal antibodies; and that 80% of children get measles before 3 years of age.  Another reason for not finding protection from measles deaths with vitamin A is the fact that measles deaths were ascertained by verbal autopsies.  Deaths associated with measles are often attributed to diarrhea or pneumonia.  A third reason for lack of effect is that there is a 2-3 year cycle of epidemic measles in India and seasonal variation in case-facilities.  Thus inclusion of children not really at risk and undercounting or misassigning causes of death may explain the results not the dosage of vitamin A.
Chromosomes of Twenty Cancer Effusions: Correlation of Karyotypic, Clinical, and Pathologic Aspects&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Takaaki Ishihara, Yasumoto Kikuchi, Avery A. Sandberg
Journal: JNCI Journal of the National Cancer Institute (1963)

The detailed chromosome constitution was determined in 20 effusions from cancer patients to try to establish karyotypic criteria for the evaluation of the material studied. All effusions were characterized by an abnormal modal number of chromosomes, ranging from 39 to 133, with no particular number more prevalent or specific for any particular tumor. In 16 effusions “new” marker chromosomes were present, but their origin could not be traced with certainty. Every effusion had a karyotype that was relatively stable over long periods but was different from that of any other effusion studied. Therapy did not appear to influence the karyotype of the effusion cells. There was no correlation between the grade of malignancy of a tumor and the karyotypic findings: modal and chromosome numbers, presence or absence of markers. The data indicate that cancer effusion cells can generate many karyotypes, and the potential significance of the genotypic changes will have to await the collection of more data. The karyotypic changes in effusion cells may not reflect those present in the original tumor.
A phase IB safety and pharmacokinetic (PK) study of recombinant human Apo2L/TRAIL in combination with rituximab in patients with low-grade non-Hodgkin lymphoma
Authors: L. Yee, M. Fanale, K. Dimick, S. Calvert, C. Robins, J. Ing, J. Ling, W. Novotny, A. Ashkenazi, H. Burris
Journal: Journal of Clinical Oncology (2007)

8078 Background: Recombinant human Apo2L/TRAIL (rhApo2L/TRAIL) induces apoptosis (programmed cell death) through binding to the pro-apoptotic receptors DR4 and DR5. Preclinical studies show that rhApo2L/TRAIL selectively induces apoptosis in many cancer cell lines derived from various malignancies including NHL, while sparing most normal cells. In vivo, rhApo2L/TRAIL and Rituximab cooperate to shrink or attenuate the growth of various NHL tumor xenografts in SCID mice. RhApo2L/TRAIL is being co-developed by Genentech and Amgen as a targeted therapy for solid tumors and hematologic malignancies. Methods: Subjects were eligible to participate if they had CD20+ follicular NHL or small lymphocytic lymphoma or marginal zone B-cell lymphoma that had progressed following stable disease or an objective response lasting &gt; 6 months duration to the most recent rituximab-contain regimen. RhApo2L/TRAIL is administered intravenously over 1 hour for 5 consecutive days every three weeks up to 4 cycles at dose levels of 4 and 8 mg/kg. Rituximab is administered intravenously at 375 mg/m 2 weekly for up to eight doses. Results: Six subjects with low grade NHL (4 with follicular NHL and 2 with small cell NHL) have been enrolled and treated with 4 mg/kg rhApo2L/TRAIL and rituximab, and one subject (with follicular NHL) has been enrolled and treated with 8 mg/kg rhApo2L/TRAIL and rituximab. The enrolled subjects range in age from 39–82 years; there are 6 male and 1 females. The number of prior therapies for NHL range from 1–8. Four subjects have received all protocol specified therapy. There have been no DLTs or SAEs or Grade 3/4 adverse events reported to date. To date, five subjects have undergone tumor response assessment: there have been 2 patients with complete response, 1 with partial response and 2 with stable disease. Conclusion: The combination of rhApo2L/TRAIL at 4 mg/kg/day and rituximab appears safe and shows evidence of activity in subjects with low grade NHL that has relapsed following previous rituximab-containing therapy. Enrollment is continuing to test rhApo2L/TRAIL at 8 mg/kg plus rituximab for expanded safety data and further dose optimization. No significant financial relationships to disclose.
Primary Tissue Culture of Human Wart-Derived Epidermal Cells (Keratinocytes)&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: M Niimura, F Pass, R Wooley, C A Soutor
Journal: JNCI Journal of the National Cancer Institute (1975)

The formation of human skin warts may depend on transformation by human papilloma virus or result from a productive virus infection. To explore this problem, methods were developed for the primary tissue culture of epidermal cells (keratinocytes) derived from wart tissues and normal skin. Wart-derived keratinocytes continued to proliferate for periods exceeding 3 months, but the patterns of cell growth were identical to normal keratinocytes. Electron microscopic and immunohistologic examination of wart-derived cultures did not evidence virion assembly.
The Susceptibility to X4 and R5 Human Immunodeficiency Virus-1 Strains of Dendritic Cells Derived In Vitro From CD34+ Hematopoietic Progenitor Cells Is Primarily Determined by Their Maturation Stage
Authors: Bruno Canque, Youssef Bakri, Sandrine Camus, Micael Yagello, Abdelaziz Benjouad, Jean Claude Gluckman
Journal: Blood (1999)
The Israeli experience with gefitinib (ZD1839) as single agent treatment of advanced non-small-cell lung cancer -a 3 years report
Authors: M. Gips, R. Catane, I. Heching, M. Levitt, O. Merimski, A. Kuten, A. Segal, M. Ben Shachar, T. Peretz
Journal: Journal of Clinical Oncology (2004)

3154 Background: For the last 3.5 years we have participated a compassionate use program of gefitinib, an orally active EGFR-TKI (epidermal growth factor receptor tyrosine kinase inhibitor), for the treatment of advanced non-small-cell lung cancer (NSCLC) as monotherapy. We herby report our experience. Methods: One hundred and eighty one patients (median age 64.0 years; M:F, 53:47%) were treated between June 2001 and November 2003. 91 (50.3%) patients reported receiving previous chemotherapy. Gefitinib (Iressa) was given as first-line treatment to elderly patients or in the presence of poor performance status or serious comorbidity. The active disease sites were lung, bones, brain, pleural effusion and liver. Treatment with gefitinib (250 mg/day) continued until disease progression or unacceptable toxicity. Results: Median duration of treatment was 60 days (range 3–304) (35% of patients were treated for >90 days). Tolerability was excellent. Mild acneiform rash and nausea were the most frequent side effects. Only 6.8% of patients discontinued treatment as a result of excessive side effects. Complete response (CR), partial response (PR), and stable disease (SD) were observed in 3/181 (1.7%), 22/181 (12.2%) and 40/181 (22.1%) of patients, respectively, giving a clinical benefit rate (CBR) of 36%. CBR was 38.5% for patients previously treated with chemotherapy. For patients treated for more than 60 days, response rate (CR+PR) was 19.3. Median duration of response was 3.5 months (range 3.0–15.0) and of SD 4.5 months. Conclusions: Gefitinib monotherapy is an effective treatment for advanced NSCLC producing a CBR of 36% both in pretreated and not treated patients. It is well tolerated even in heavily pretreated, elderly patients and or in the presence of serious comorbidity. 50.8% of patients were treated for <2 months, which might be too short to be effective. It is possible that a higher response rate could be achieved if gefitinib had been started immediately after previous chemotherapy, rather than after further disease progression. Gefitinib offers patients with NSCLC an effective modality where other options hardly exist. No significant financial relationships to disclose.
Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.
Authors: N M Marina, J Rodman, S J Shema, L C Bowman, E Douglass, W Furman, V M Santana, M Hudson, J Wilimas, W Meyer
Journal: Journal of Clinical Oncology (1993)

PURPOSE The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors. PATIENTS AND METHODS To reduce interpatient variability in carboplatin systemic exposure, 45 children were treated with doses individualized to a target area under the serum concentration versus time curve (AUC) based on renal function, using technetium 99-diethyl-enetriamine pentaacetic acid (99mTc-DTPA) clearance to estimate glomerular filtration rate (GFR). Cohorts of at least three patients received carboplatin at an initial target AUC of 2 mg/mL x min, with escalations of 1 mg/mL x min in subsequent cohorts. Courses consisted of carboplatin on day 1 followed by IFOS 2 g/m2 plus VP-16 100 mg/m2 on days 2 and 3. Patients received at least two courses, with a maximum of eight courses possible in the absence of progressive disease. When only moderate toxicity occurred after escalation to 5 mg/mL x min, a third dose of IFOS plus VP-16 was added. After three patients were treated at this level, carboplatin escalation proceeded. RESULTS Neutropenia and thrombocytopenia were the dominant toxicities in the 43 assessable patients. At the target AUC of 8 mg/mL x min, 13 of 20 cycles were associated with febrile neutropenia. For phase II trials, we recommend a carboplatin target AUC of 6 mg/mL x min with three doses of IFOS and VP-16 for patients with prior craniospinal irradiation or high-dose cisplatin (CDDP)/VP-16, or 7 mg/mL x min for patients without such histories. There were two complete responses (CRs), 13 partial responses (PRs), and 17 objective responses (ORs). CONCLUSION The ICE regimen shows promising activity in pediatric solid tumors. The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy.
HTLV-III/LAV Seroconversion Following a Deep Intramuscular Needlestick Injury
Authors: R L Stricof, D L Morse
Journal: New England Journal of Medicine (1986)

The authors report a case of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) seroconversion after an occupational injury.  The subject a female health care worker in the US received a deep intramuscular needlestick injury with a large-bore unit that was visibly contaminated with blood from a patient with acquired immunodeficiency syndrome (AIDS).  14 days after injury fever chills myalgias and arthralgias developed.  Examination revealed an enlarged right axillary lymph node.  On day 17 an erythematous macular rash appeared on the abdomen and lasted 5 days.  The health care worker continued to have cramps diarrhea and weight loss.  A diagnosis of Clostridium difficile colitis was made and oral vancomycin therapy was followed by a complete resolution of symptoms.  Since then the health worker has had intermittent oral candidiasis a persistent postcervical lymph node and transient enlargement of suboccipital and inguinal lymph nodes.  Serum collected 9 days after the injury was negative for HTLV-III/LAV antibody but samples collected on days 184 and 239 were positive.  The health workers husband was seronegative when tested 239 days after injury.  The results of virus culture for HTLV-III/LAV performed on blood from both the health care worker and her husband were negative at 239 days.  The only 2 documented cases of HTLV-III/LAV antibody seroconversion in health care workers have occurred after highly unusual parenteral exposure to blood.  In the other case blood from an AIDS patient may have been injected into a health care workers finger.  These 2 cases emphasize the need for strict adherence to recommended infection control precautions especially those regarding the handling of needles and other sharp objects.