Caring for sexual and gender minority patients with genitourinary cancer: A primer for inclusive practices.

Recognizing sexual orientation and gender identity (SOGI) is paramount in the management of genitourinary cancers, as sexual and gender minority (SGM) individuals encounter unique healthcare challenges leading to disparities. SGM patients often confront systemic barriers, provider biases, and scarcity of tailored resources, resulting in diminished satisfaction and adverse health outcomes. The evaluation and treatment of genitourinary cancers in SGM patients demand a nuanced, multidisciplinary approach that focuses on the unique health determinants often overlooked by the healthcare system. This review highlights recommendations for the inclusivity of SGM patients within the clinic, from inclusive signage to gender inclusive language. For the evaluation and treatment of SGM patients with genitourinary cancers, it is recommended to employ organ-based language, to utilize validated questionnaires encompassing mental health, sexual behavior, and patient-reported outcomes, and to provide timely referrals to social work and onco-fertility when appropriate. Ultimately, approaching inclusivity through education targeted at both SGM patients and healthcare providers is pivotal for centering care around the patient, improving the quality of life and outcomes for SGM patients facing genitourinary cancers.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Mapping geographic disparities in treatment and clinical outcomes of high-grade aneurysmal subarachnoid hemorrhage in the United States.

BACKGROUND AND OBJECTIVE: Although high-grade (Hunt and Hess 4 and 5) aneurysmal subarachnoid hemorrhage (aSAH) typically portends a poor prognosis, early and aggressive treatment has previously been demonstrated to confer a significant survival advantage. This study aims to evaluate geographic, demographic, and socioeconomic determinants of high-grade aSAH treatment in the United States. METHODS: The National Inpatient Sample (NIS) was queried to identify adult high-grade aSAH hospitalizations during the period of 2015 to 2019 using the International Classification of Diseases, 10th Revision, Clinical Modification (ICD) codes. The primary clinical endpoint of this analysis was aneurysm treatment by surgical or endovascular intervention (SEI), while the exposure of interest was geographic region by census division. Favorable functional outcome (assessed by the dichotomous NIS-SAH Outcome Measure, or NIS-SOM) and in-hospital mortality were evaluated as secondary endpoints in treated and conservatively managed groups. RESULTS: Among 99 460 aSAH patients identified, 36 795 (37.0%) were high-grade, and 9210 (25.0%) of these were treated by SEI. Following multivariable logistic regression analysis, determinants of treatment by SEI included female sex (adjusted OR (aOR) 1.42, 95% CI 1.35 to 1.51), transfer admission (aOR 1.18, 95% CI 1.12 to 1.25), private insurance (ref: government-sponsored insurance) (aOR 1.21, 95% CI 1.14 to 1.28), and government hospital ownership (ref: private ownership) (aOR 1.17, 95% CI 1.09 to 1.25), while increasing age (by decade) (aOR 0.93, 95% CI 0.91 to 0.95), increasing mortality risk (aOR 0.60, 95% CI 0.57 to 0.63), urban non-teaching hospital status (aOR 0.66, 95% CI 0.59 to 0.73), rural hospital location (aOR 0.13, 95% CI 0.7 to 0.25), small hospital bedsize (aOR 0.68, 95% CI 0.60 to 0.76), and geographic region (South Atlantic (aOR 0.72, 95% CI 0.63 to 0.83), East South Central (aOR 0.75, 95% CI 0.64 to 0.88), and Mountain (aOR 0.72, 95% CI 0.61 to 0.85)) were associated with a lower likelihood of treatment. High-grade aSAH patients treated by SEI experienced significantly greater rates of favorable functional outcomes (20.1% vs 17.3%; OR 1.20, 95% CI 1.13 to 1.28, P<0.001) and lower rates of mortality (25.8% vs 49.1%; OR 0.36, 95% CI 0.34 to 0.38, P<0.001) in comparison to those conservatively managed. CONCLUSION: A complex interplay of demographic, socioeconomic, and geographic factors influence treatment patterns of high-grade aSAH in the United States.

High-quality read-based phasing of cystic fibrosis cohort informs genetic understanding of disease modification.

Phasing of heterozygous alleles is critical for interpretation of cis-effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of CFTR haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of CFTR haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a PRSS2 missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are PRSS2 pancreas eQTLs (p = 9.5 × 10-7 and p = 1.4 × 10-4, respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute.

Computing contact angles for oil-water-rock systems via thermodynamic integration.

Wettability of rock surfaces with respect to oil and water, which is characterized by the contact angle, is an important factor that determines the efficacy of enhanced oil recovery operations. Experimental determination of contact angles for oil-water-rock systems is expensive and time-consuming due to the extremely long times needed for the establishment of adsorption equilibrium at the liquid-solid interface. Hence, molecular simulations form an attractive tool for computing contact angles. In this work, we use the cleaving wall technique that was developed previously in our group [R. K. R. Addula and S. N. Punnathanam, J. Chem. Phys. 153, 154504 (2020)] to compute solid-liquid interfacial free energy, which is then combined with Young's equation to compute the oil-water contact angle on silica surfaces. The silica surface is modeled with the INTERFACE force field that has been developed to accurately reproduce experimental data. We have considered three different surface chemistries of silica, namely, Q2, Q3, and Q4, in this study. Our calculations reveal that while the Q2 and Q3 surfaces are completely wetted by water, the Q4 surface is partially non-wetted by water. All the simulations needed for this calculation can be performed using the Large-scale Atomic/Molecular Massively Parallel Simulator (LAMMPS) molecular package. This should facilitate wider adoption of the Young's equation route to compute contact angles for systems comprised of complex molecules.

Disaggregation of Asian American and Pacific Islander Women With Stage 0-II Breast Cancer Unmasks Disparities in Survival and Surgery-to-Radiation Intervals: A National Cancer Database Analysis From 2004 to 2017.

PURPOSE: Aggregation of Asian Americans (AAs) with Native Hawaiians and Other Pacific Islanders (NHPIs) masks significant health disparities. We evaluated overall survival (OS) and surgery-to-radiation intervals (STRIs) among AA and NHPI women with early-stage breast cancer. METHODS: This National Cancer Database study included women with stage 0-II breast cancer diagnosed between 2004 and 2017. STRI was defined as days from surgery to radiation. Patients were stratified by adjuvant treatment. AAs were disaggregated into geographically relevant subpopulations: East, South, and Southeast Asians. Kaplan-Meier estimates and log-rank tests assessed survival. Cox proportional hazard and linear regression were adjusted for clinical and sociodemographic factors. RESULTS: In total, 578,927 women were included (median age 61 years, median follow-up 65 months, and 10-year OS 83%). AA and NHPI 10-year OS was 91% overall; subpopulation 10-year OS was 92% for East Asian, 90% for South Asian, 90% for Southeast Asian, and 83% for NHPI. On multivariable analysis, compared with non-Hispanic White, NHPI women had worse survival (adjusted hazard ratio [aHR] = 1.38; 95% CI, 1.09 to 1.77); all AA subpopulations had improved survival: East Asian (aHR = 0.57; 95% CI, 0.48 to 0.69), South Asian (aHR = 0.66; 95% CI, 0.51 to 0.84), and Southeast Asian (aHR = 0.78; 95% CI, 0.65 to 0.94). The AA and NHPI median STRI for was 73 days overall; the disaggregated median STRI was 68 days for East Asian, 80 days for South Asian, 77 days for Southeast Asians, and 81 days for NHPI. On adjusted analysis, compared with non-Hispanic White, Southeast Asians and NHPI had longer STRI by 6.6 (95% CI, 4.3 to 8.9) and 10.0 (95% CI, 5.8 to 14) days, respectively. CONCLUSION: Breast cancer disparities exist among disaggregated AA and NHPI subpopulations. Data disaggregation insights may lead to interventions to overcome these disparities, such as optimizing time-to-treatment for select populations.

Autonomic Dysreflexia After Hip Fractures Managed by Regional Anesthesia: A Case Report.

Autonomic dysreflexia occurs after a spinal cord injury usually at the level of T6 or above, and its hallmark feature is exaggerated autonomic response to noxious stimuli resulting in uncontrolled hypertensive episodes with reflexive bradycardia that can be fatal if not controlled. We present a case highlighting regional anesthetic techniques, including peripheral nerve blocks, to ameliorate the symptoms of autonomic dysreflexia triggered by hip fractures in a 57-year-old woman with an old C5-C6 spinal cord injury before definitive hip surgery. The regional techniques described provide anesthesiologists with a simple strategy to potentially mitigate a life-threatening situation.

Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.

BACKGROUND: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease so that effective therapies can be developed. The majority of pre-clinical studies evaluating skeletal muscle's response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. METHODS: To create four cohorts of PDX mice evaluated in this study, tumours resected from four pancreatic ductal adenocarcinoma patients were portioned and attached to the pancreas of immunodeficient NSG mice. RESULTS: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumour burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA also revealed key differences between their transcriptomes in response to cancer. Genes up-regulated in the DIA were enriched for extracellular matrix protein-encoding genes and genes related to the inflammatory response, while down-regulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed up-regulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis, and down-regulation of genes encoding extracellular matrix proteins. CONCLUSIONS: These data suggest that distinct biological processes may account for wasting in different skeletal muscles in response to the same tumour burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.

Laboratory Evaluation of Spasmodic Dysphonia.

OBJECTIVES: To evaluate the utility of comprehensive laboratory evaluation in patients with spasmodic dysphonia (SD). STUDY DESIGN: Retrospective chart review. METHODS: A review of the medical records of 40 patients diagnosed with spasmodic dysphonia from 2009-2018 was preformed to evaluate abnormal test results that were significant when compared with abnormal results of the general population and for any other clinically relevant pathology. RESULTS: Erythrocyte sedimentation rate, ceruloplasmin levels, and anti-AChR were found to be elevated at levels considered statistically significant (p <0.05). Furthermore, we found levels of cholesterol, thyroid-stimulating hormone (TSH), T3, fasting blood glucose, creatine kinase, immunoglobulin, antinuclear antibody (ANA), and alpha-fetoprotein (AFP) levels to be abnormal at a greater rate in our population, but these were not statistically significant. Workup revealed several underlying conditions including thyroid neoplasms, hypothyroidism, and laryngopharyngeal reflux. Additionally, brain MRI revealed age-related ischemic pathology in an elevated number of patients, but with no obvious clinical sequalae. CONCLUSION: There is an association between serological values and spasmodic dysphonia that can aid in diagnosing pathology, as well as establishing a directed workup. Additionally, our study shows the utility of comprehensive evaluation in identifying undetected disease.

IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.

Tumor-derived cytokines are known to drive the catabolism of host tissues, including skeletal muscle. However, our understanding of the specific cytokines that initiate this process remains incomplete. In the current study, we conducted multiplex analyte profiling of cytokines in conditioned medium (CM) collected from human pancreatic cancer (PC) cells, human tumor-associated stromal (TAS) cells, and their co-culture. Of the factors identified, interleukin-8 (IL-8) is released at high levels from PC cells and PC/TAS co-culture and has previously been associated with low muscle mass in cancer patients. We, therefore, treated C2C12 myotubes with IL-8 which led to the activation of ERK1/2, STAT, and Smad signaling, and induced myotube atrophy. Moreover, the treatment of mice with IL-8 also induced significant muscle wasting, confirming the in vivo relevance of IL-8 on muscle. Mechanistically, IL-8-induced myotube atrophy is inhibited by treatment with the CXCR2 antagonist, SB225002, or by treatment with the ERK1/2 inhibitor, U0126. We further demonstrate that this axis mediates muscle atrophy induced by pancreatic cancer cell CM, as neutralization of IL-8 or treatment with SB225002 or U0126 significantly inhibit CM-induced myotube atrophy. Thus, these data support a key role of IL-8 released from human PC cells in initiating atrophy of muscle cells via CXCR2-ERK1/2.​.

A prospective study assessing feasibility of performing percutaneous nephrolithotomy in chronic kidney disease patients - What factors affect the outcome?

ABSTRACT Objectives To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. Materials and Methods Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR<60/s.creatinine>2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0-2] were included in the study. Results A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not significant enough to cause stage migration. Again 3 (17.65%) , 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not significant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the final follow up visit (6 months). Conclusion Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.

A prospective study assessing feasibility of performing percutaneous nephrolithotomy in chronic kidney disease patients - What factors affect the outcome?

OBJECTIVES: To primarily evaluate the functional outcomes of PCNL for bilateral renal calculi/calculi in solitary functioning kidney with Chronic Kidney Disease(CKD). To identify factors affecting the renal replacement therapy following PCNL. MATERIALS AND METHODS: Patients with bilateral renal calculi/calculi in solitary kidney and CKD (eGFR<60/s.creatinine>2) and Good Performance Status [Eastern Cooperative Oncology Group (ECOG): 0-2] were included in the study. RESULTS: A total of 60 patients with CKD who had bilateral renal calculi/calculi in solitary functioning kidney underwent PCNL. At 6 months, eGFR improved or stabilized in 45 (75%) patients, while in 15 (25%) patients eGFR deteriorated. A total of 5 (14.28%) and 2 (25%) patients of CKD stage 4 and 5 respectively had improvement in eGFR as well as CKD stage. Fourteen (82.35%), 21 (60%), 3 (37.5%) patients of CKD stage 3, 4, 5 had improvement in eGFR but not signifi cant enough to cause stage migration. Again 3 (17.65%), 9 ( 40%) and 3 (37.5%) patients of CKD stage 3, 4, 5 had reduction in eGFR but not signifi cant enough to cause stage migration. None of the patients had worsening of CKD stage. Preoperative CKD stage and eGFR were compared with measurements made at the fi nal follow up visit (6 months). CONCLUSION: Our results indicate that most patients of renal calculi with CKD show improvement or stabilization of renal function with aggressive stone removal. Improvement is more in patients who have mild to moderate CKD. Aggressive management of comorbidities, peri-operative UTI and complications may delay or avoid progression of CKD status in such patients.

National trends in surgical therapy for benign prostatic hyperplasia in Australia.

BACKGROUND: To determine national trends in the utilization of surgical procedures for the treatment of benign prostatic hyperplasia (BPH) in Australia over the last 20 years. METHODS: The Medicare Australia and Australian Institute of Health and Welfare databases were used to determine the annual number of surgical procedures and hospital admissions for BPH. RESULTS: From 1998 to 2017, surgical procedures for BPH have increased by 79% which is largely commensurate with population growth. From 1998 to 2008, transurethral resection of the prostate (TURP) was the predominant surgical therapy, accounting for 96% of all surgical treatments. From 2008 to 2017, TURP use reduced to 70% and in the last 5 years has been replaced with photoselective vaporization (16%), UroLift (8%) and holmium laser prostatectomy (6%). UroLift is used significantly more in younger men (P < 0.001). CONCLUSION: There has been a substantial increase in surgical treatments for BPH over the last 20 years. In the last 5 years, TURP use has declined due to an increase in laser prostatectomy and UroLift procedures.

The Personal Genome Project Canada: findings from whole genome sequences of the inaugural 56 participants.

BACKGROUND: The Personal Genome Project Canada is a comprehensive public data resource that integrates whole genome sequencing data and health information. We describe genomic variation identified in the initial recruitment cohort of 56 volunteers. METHODS: Volunteers were screened for eligibility and provided informed consent for open data sharing. Using blood DNA, we performed whole genome sequencing and identified all possible classes of DNA variants. A genetic counsellor explained the implication of the results to each participant. RESULTS: Whole genome sequencing of the first 56 participants identified 207 662 805 sequence variants and 27 494 copy number variations. We analyzed a prioritized disease-associated data set (n = 1606 variants) according to standardized guidelines, and interpreted 19 variants in 14 participants (25%) as having obvious health implications. Six of these variants (e.g., in BRCA1 or mosaic loss of an X chromosome) were pathogenic or likely pathogenic. Seven were risk factors for cancer, cardiovascular or neurobehavioural conditions. Four other variants - associated with cancer, cardiac or neurodegenerative phenotypes - remained of uncertain significance because of discrepancies among databases. We also identified a large structural chromosome aberration and a likely pathogenic mitochondrial variant. There were 172 recessive disease alleles (e.g., 5 individuals carried mutations for cystic fibrosis). Pharmacogenomics analyses revealed another 3.9 potentially relevant genotypes per individual. INTERPRETATION: Our analyses identified a spectrum of genetic variants with potential health impact in 25% of participants. When also considering recessive alleles and variants with potential pharmacologic relevance, all 56 participants had medically relevant findings. Although access is mostly limited to research, whole genome sequencing can provide specific and novel information with the potential of major impact for health care.

Ligand-dependent cholesterol interactions with the human A(2A) adenosine receptor.

We present nearly 10 µs of all-atom simulation data of a G-protein coupled receptor, the human A2A adenosine receptor, bound to four different ligands. Our focus is on binding of cholesterol to the "cholesterol consensus motif," a cluster of five amino acids on the second and fourth transmembrane helices, which interact with two cholesterols in the intracellular leaflet of the bilayer. We find evidence for a ligand-specific interaction between the CCM and cholesterol, mediated by the rotameric dynamics and configuration of Trp129. Binding of the synthetic agonist UK432097 disrupts hydrogen bonding between Trp129 and Ser47, which activates the rotameric dynamics of Trp129 and disrupts the interaction with one of the two cholesterols. We also investigate the effect of four thermostabilizing mutations, three of which are located on helix two. The conformational stability of helix two has been proposed to be sensitive to interaction with cholesterol in the CCM, suggesting a mechanism for the thermostabilization. However, our data are instead suggestive of a force-field dependent "straightening" of helix two, and therefore offer no basis for rationalizing the effect of the quadruple mutant.

Improvement of N-glycan site occupancy of therapeutic glycoproteins produced in Pichia pastoris.

Yeast is capable of performing posttranslational modifications, such as N- or O-glycosylation. It has been demonstrated that N-glycans play critical biological roles in therapeutic glycoproteins by modulating pharmacokinetics and pharmacodynamics. However, N-glycan sites on recombinant glycoproteins produced in yeast can be underglycosylated, and hence, not completely occupied. Genomic homology analysis indicates that the Pichia pastoris oligosaccharyltransferase (OST) complex consists of multiple subunits, including OST1, OST2, OST3, OST4, OST5, OST6, STT3, SWP1, and WBP1. Monoclonal antibodies produced in P. pastoris show that N-glycan site occupancy ranges from 75-85 % and is affected mainly by the OST function, and in part, by process conditions. In this study, we demonstrate that N-glycan site occupancy of antibodies can be improved to greater than 99 %, comparable to that of antibodies produced in mammalian cells (CHO), by overexpressing Leishmania major STT3D (LmSTT3D) under the control of an inducible alcohol oxidase 1 (AOX1) promoter. N-glycan site occupancy of non-antibody glycoproteins such as recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) was also significantly improved, suggesting that LmSTT3D has broad substrate specificity. These results suggest that the glycosylation status of recombinant proteins can be improved by heterologous STT3 expression, which will allow for the customization of therapeutic protein profiles.

Glycoengineered Pichia produced anti-HER2 is comparable to trastuzumab in preclinical study.

Mammalian cell culture systems are used predominantly for the production of therapeutic monoclonal antibody (mAb) products. A number of alternative platforms, such as Pichia engineered with a humanized N-linked glycosylation pathway, have recently been developed for the production of mAbs. The glycosylation profiles of mAbs produced in glycoengineered Pichia are similar to those of mAbs produced in mammalian systems. This report presents for the first time the comprehensive characterization of an anti-human epidermal growth factor receptor 2 (HER2) mAb produced in a glycoengineered Pichia, and a study comparing the anti-HER2 from Pichia, which had an amino acid sequence identical to trastuzumab, with trastuzumab. The comparative study covered a full spectrum of preclinical evaluation, including bioanalytical characterization, in vitro biological functions, in vivo anti-tumor efficacy and pharmacokinetics in both mice and non-human primates. Cell signaling and proliferation assays showed that anti-HER2 from Pichia had antagonist activities comparable to trastuzumab. However, Pichia-produced material showed a 5-fold increase in binding affinity to FcγIIIA and significantly enhanced antibody dependant cell-mediated cytotoxicity (ADCC) activity, presumably due to the lack of fucose on N-glycans. In a breast cancer xenograft mouse model, anti-HER2 was comparable to trastuzumab in tumor growth inhibition. Furthermore, comparable pharmacokinetic profiles were observed for anti-HER2 and trastuzumab in both mice and cynomolgus monkeys. We conclude that glycoengineered Pichia provides an alternative production platform for therapeutic mAbs and may be of particular interest for production of antibodies for which ADCC is part of the clinical mechanism of action.