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Purpose: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities., Methods: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t -tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t -test., Results: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups., Conclusion: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors., Competing Interests: Debra L. BartonResearch Funding: Merck Stephanie L. PughResearch Funding: Pfizer (Inst), Millennium (Inst) Patricia A. GanzLeadership: Intrinsic LifeSciences (I)Stock and Other Ownership Interests: Xenon Pharma (I), Intrinsic LifeSciences (I), Teva, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott LaboratoriesConsulting or Advisory Role: InformedDNA, Vifor Pharma (I), Ambys Medicines (I), Global Blood Therapeutics (I), GlaxoSmithKline (I), Ionis Pharmaceuticals (I), Protagonist Therapeutics (I), Akebia Therapeutics (I), Regeneron (I), Sierra Oncology (I), Rockwell Medical Technologies Inc (I), Astellas Pharma (I), Gossamer Bio (I), American Regent (I), Disc Medicine (I), Blue Note Therapeutics (I), Grail (I)Research Funding: Blue Note Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease, UpToDate royalties for section editor on survivorshipTravel, Accommodations, Expenses: Intrinsic LifeSciences (I) Steven C. PlaxeStock and Other Ownership Interests: Pfizer, Merck, Zimmer Biomet, GlaxoSmithKline, AstraZeneca, Bristol Myers Squibb/Pfizer, Johnson & Johnson/JanssenResearch Funding: Endocyte, Incyte, MedImmune, Novartis, Pfizer, Janssen Oncology, BIND Therapeutics, PharmaMar, AstraZeneca, Kevelt, Millennium, Tesaro Bridget F. KoontzEmployment: GenesisCareLeadership: GenesisCareConsulting or Advisory Role: Blue Earth Diagnostics, Myovant Sciences, Rythera TherapeuticsResearch Funding: Janssen, Merck, Blue Earth DiagnosticsPatents, Royalties, Other Intellectual Property: Demos Publishing Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava SciencesOpen Payments Link: https://openpaymentsdata.cms.gov/physician/820072 Carolyn Y. MullerResearch Funding: AstraZeneca, Genmab, VBL Therapeutics, Roche/Genentech, TapImmune Inc, Linnaeus Therapeutics, Agenus, Incyte, MerckPatents, Royalties, Other Intellectual Property: Have a pending patent on the cancer use for R-ketorolac—not yet its own new drugOther Relationship: NCI, Department of Defense Lisa A. KachnicConsulting or Advisory Role: New B InnovationResearch Funding: Varian Medical SystemsPatents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

Modified colloids and flat surfaces occupy an important place in materials science research due to their widespread applications. Interest in the development of modifiers that adhere strongly to surfaces relates to the need for stability under ambient conditions in many applications. Diazonium salts have evolved as the primary choice for the modification of surfaces. The term "diazonics" has been introduced in the literature to describe "the science and technology of aryldiazonium salt-derived materials". The facile reduction of diazonium salts via chemical or electrochemical processes, irradiation stimuli, or spontaneously results in the efficient modification of gold surfaces. Robust gold-aryl nanoparticles, where gold is connected to the aryl ring through bonding to carbon and films modified by using diazonium salts, are critical in electronics, sensors, medical implants, and materials for power sources. Experimental and theoretical studies suggest that gold-carbon interactions constructed via chemical reactions with diazonium salts are stronger than nondiazonium surface modifiers. This invited feature article summarizes the conceptual development of recent studies of diazonium salts in our laboratories and others with a focus on the surface modification of gold nanostructures, flat surfaces and gratings, and their applications in nanomedicine engineering, sensors, energy, forensic science, and catalysis.

Lynch syndrome patients with synchronous endometrial and ovarian cancer (SEOC) are rare. When these cases occur, they are most often endometrioid histology and early grade. Early-grade tumors are not often sent for somatic tumor profiling. We present a 39 year old SEOC patient with germline PMS2 Lynch syndrome and clinical tumor analysis leading to insight regarding the origin and cause of these tumors, with potential therapy options. PMS2 -related SEOC is less common due to lower risks for these cancers associated with germline PMS2 mutation compared to other Lynch genes. While synchronous cancers are not common, they are more likely to occur with Lynch syndrome. Tumor profiling with next-generation sequencing of 648 genes identified sixteen shared somatic actionable and biologically relevant mutations. This case is a rare example of a patient with PMS2 germline Lynch syndrome with shared somatic variants that demonstrate clonality of the two tumors arising from one common site.

Drawing on 10 years of followership instruction, this chapter explores the authors' methodology for immersing federal employees and graduate students in discussions about followership and the follower role as a means of enhancing workplace engagement and furthering mission objectives. Our practice has found that when participants explore the tenets of followership from an engagement perspective, perceptions of followers being in subservient obedience to leader authority transition into conceptualizations of a mission-focused partnership with the leader., (© 2020 Wiley Periodicals LLC.)

Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of breast cancer. However, there is great variation in this increase in risk with several genetic and non-genetic modifiers identified. The BRCA1 protein plays a central role in DNA repair, a mechanism that is particularly instrumental in safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that alter the expression and/or function of BRCA1 carried on the wild-type (non-mutated) copy of the BRCA1 gene would modify the risk of breast cancer in carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003). Promoter in vitro assays of the major BRCA1 haplotypes showed that common polymorphisms in the regulatory region alter its activity and that this effect may be attributed to the differential binding affinity of nuclear proteins. In conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1 transcription.

Objective: To identify factors associated with persistence or clearance of cervical intraepithelial neoplasia (CIN) following loop electrosurgical excision procedure (LEEP) in high-risk patients., Study Design: In a retrospective database review, we identified 343 patients who had 2 LEEP procedures or LEEP followed by hysterectomy for CIN at Grady Memorial Hospital. We compared margin status, endocervical curettage (ECC) at LEEP and follow-up cytology for patients characterized as having persistent or nonpersistent dysplasia., Results: Seventy-nine percent (71/90) of patients with positive LEEP margins had persistent disease vs. 50% (45/90) with negative margins (odds ratio [OR]=3.7, 95% confidence interval [CI] 1.9-7.2, P<.0001). Ninety-one percent (29/32) with positive margins and positive ECC had persistent disease vs. 47% (26/55) with negative margins and negative ECC (OR=10.8, 95% CI 2.9-39.6, P<.0001). Sixty-eight percent (149/218) with at least 1 positive Pap smear following LEEP had persistent disease vs. 37% (11/30) with all negative follow-up Pap smears (OR = 3.7, 95% CI 1.7-8.3, P = .0007)., Conclusion: Although the risk of persistent CIN increased with positive LEEP margins, ECC and cytology, these variables, when negative, offered no ensurance of a future disease-free state in this high-risk population.

Cervical carcinoma is prevented easily with proper screening. Unfortunately, many women in industrialized countries continue to have poor access to adequate medical care. In many third-world countries, cervical cancer is one of the top malignancies diagnosed. Screening should be provided for all women to prevent or diagnose cervical cancer at an early, treatable stage.

Background: The purpose of this study was to compare the clinical characteristics of endometrial carcinomas with and without microsatellite instability (MSI)., Methods: The authors prospectively acquired DNA from patients with endometrial carcinomas at Washington University Medical Center. Tumors were assigned MSI (+) status when two or more of five microsatellite repeat markers revealed novel bands in tumor DNA not present in the corresponding normal DNA. Clinical characteristics and survival data of patients with and without MSI were abstracted from patient charts. Statistical significance was calculated with the chi-square test, and survival was assessed with Kaplan-Meier methods., Results: The authors found 65 of 70 (93%) patients with MSI (+) tumors to be of white race, whereas only 124 of 159 (78%) patients with MSI (-) tumors were white (P = 0.012). Advanced disease (International Federation of Gynecology and Obstetrics Stage III-IV) was observed in 9 of 70 (13%) MSI (+) patients and 44 of 159 (28%) MSI (-) patients (P = 0.017). In addition, aggressive histologic subtypes were observed less frequently in MSI (+) tumors (6/70 [8%]) than in MSI (-) tumors (30 of 159 [19%]) (P = 0.034). Race and stage were shown by multivariate analysis to be different in MSI (+) and MSI (-) patients. Recurrence and overall survival were similar in the two groups., Conclusions: Patients with MSI (+) tumors were more likely to be of white race and to present with early stage disease. Further investigation is needed to explain why patients with MSI (+) tumors have similar survival to patients with MSI (-) tumors, despite presenting at earlier stages, being of white race, and being less likely to be associated with virulent histologic subtypes., (Copyright 2000 American Cancer Society.)

Objective: PTEN, a tumor suppressor gene shown to be frequently mutated in endometrial cancers, has been suggested to be a target of microsatellite instability (MSI)-driven mutagenesis. We set out to investigate the relationship between MSI and PTEN mutation in a large series of primary endometrial carcinomas., Methods: Thirty-nine MSI-positive endometrial cancers were evaluated by single-strand conformational variant analysis and direct sequencing to screen all nine PTEN exons for mutation., Results: Fifteen specimens (38%) demonstrated 16 PTEN mutations. We observed only one alteration in the poly-adenine repeat of exon 8 that is suggested to be a target for mutation in endometrial cancers with MSI. Seven of 16 (44%) mutations in our series were deletions of >/=3 bp, a class of mutation not usually associated with tumors with defective DNA mismatch repair. To determine the significance of this high frequency of deletion, 26 additional endometrial cancers without MSI were matched with the 39 MSI-positive cancers for the prognostic factors of tumor histology, stage, grade, and patient race. The MSI-positive tumors had a significantly higher frequency of deletions involving >/=3 bp when compared with the MSI-negative group (5/11 versus 0/10, P = 0.035)., Conclusions: Repeat tract mutation in PTEN is an uncommon event in MSI-positive cancers. Deletion of >/=3 bp in this gene is more common in MSI-positive cancers when compared with tumors without MSI., (Copyright 2000 Academic Press.)

Family history plays an important role in breast, ovarian, and colorectal cancers. The increasing availability of genetic testing has forced women with these malignancies and their physicians to confront new questions regarding screening and prevention. This review highlights the screening for and prevention of breast, ovarian, and colorectal cancer in women at risk for malignancy.

Objective: Approximately 20% of endometrial tumors have a defect in DNA mismatch repair and exhibit microsatellite instability (MSI). We assessed the role of the PMS2 DNA mismatch repair gene in MSI-positive sporadic endometrial tumors., Methods: We examined 40 sporadic endometrial tumor specimens with MSI. All 15 exons of the PMS2 gene were investigated for sequence alterations by single-strand conformational variant analysis., Results: Twelve polymorphisms were identified, 8 of which were in the coding sequence. Four specimens revealed mutations in intronic sequences that are not predicted to affect the PMS2 mRNA. No mutations were detected within the coding region of the PMS2 gene., Conclusion: We conclude that structural mutations in the PMS2 gene are not responsible for defective DNA mismatch repair in sporadic endometrial cancers with MSI. The identification of single nucleotide polymorphisms in the PMS2 locus may aid in the mapping and characterization of genetic diseases., (Copyright 1999 Academic Press.)

Background: Up to 20% of ovarian epithelial tumors are classified as being of low malignant potential. Most of these low malignant potential tumors are detected at an early stage and have an excellent prognosis. This is a report of a woman with cardiac metastasis from an ovarian low malignant potential tumor., Case: This case describes a 53-year-old woman who presented with congestive heart failure and was found to have a recurrent stage III ovarian tumor of low malignant potential. A transesophageal echocardiogram revealed compression of the inferior vena cava and a mass encompassing the right atrium. Findings at autopsy confirmed a low malignant potential ovarian tumor thrombus involving the inferior vena cava and right atrium., Conclusion: Ovarian low malignant potential tumors can metastasize in an aggressive manner. A transesophageal echocardiogram may be useful when the diagnosis of cardiac tumor thrombus is considered.

Vitamin A (retinol) is needed by higher animals for the maintenance of normal epithelium and growth, and retinoic acid (I) has been proposed to be the active metabolite. Microbial models are useful for the study of mammalian metabolism of xenobiotics. Two species of the fungal genus Cunninghamella afforded products of greater polarity than 1 when fed 1 in a two-stage fermentation procedure. The products obtained were principally the result of oxidation of the trimethylcyclohexenyl ring. Although most of the isolated metabolites of 1 have been previously seen in mammalian studies, two novel compounds, 2-hydroxyretinoic acid (2) and 2,3-dehydro-4-oxoretinoic acid (4), were isolated.