Comparative Evaluation of DFDBA versus PRF with DFDBA in Treatment of Grade-II Furcation Defects - A Clinical Trial.

Background: In order to determine whether a method is more successful for treating a grade-II furcation deficiency, this randomized trial will compare demineralized freeze-dried bone allograft (DFDBA) to platelet-rich fibrin with DFDBA. Materials and Methods: Twenty systematically healthy patients between the ages of 30 and 60 with a grade-II furcation were evaluated pre and postoperatively for changes in the modified plaque index, probing depth, relative vertical and horizontal clinical attachment level, gingival marginal level, and radiographic bone defect. Results: The test group significantly outperformed the control group on all clinical and radiological measures. Conclusion: The experimental group improved at both clinical attachment levels and had a higher decrease in probing depth than the control group did.

Connecting Bisphenol A Exposure to PCOS: Findings from a Case-Control Investigation.

Polycystic Ovary Syndrome (PCOS) is a multifaceted condition influenced by genetic, hormonal, and environmental factors. Among environmental factors, Bisphenol A (BPA)-a recognized endocrine disruptor-has been implicated in the development of PCOS. The study aimed to compare BPA levels in women diagnosed with PCOS with those in healthy controls, using the high-performance liquid chromatography (HPLC) technique. The study involved 80 women diagnosed with PCOS and 50 healthy control participants. Demographic and biochemical parameters were recorded, including age, Body Mass Index (BMI), and levels of testosterone, estradiol, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Dehydroepiandrosterone Sulfate (DHEA-S), Thyroid Stimulating Hormone (TSH), and Insulin Resistance as measured by the Homeostatic Model Assessment (HOMA-IR). Furthermore, BPA levels were measured using the HPLC technique. Women with PCOS exhibited significantly higher mean age and BMI compared to healthy controls (p = 0.01, p < 0.0001, respectively). Additionally, higher levels of testosterone (p = 0.04), LH (p = 0.03) and BPA (p < 0.0001) were observed in women with PCOS. However, estradiol, FSH, PRL, LH/FSH ratio, DHEA-S, and TSH levels were not significantly different between the two groups. HOMA-IR levels were not recorded for the control group. A notable positive relationship emerged between Bisphenol A and luteinizing hormone (LH) levels (r = 0.23, p = 0.03), also significant negative correlation appeared between Bisphenol A and thyroid-stimulating hormone (TSH) levels. This study found that women with PCOS have elevated BPA levels compared with healthy controls, showing a need for further research on the relationship between BPA exposure and the development of PCOS.

Endocrine-disrupting chemicals and hormonal profiles in PCOS women: A comparative study between urban and rural environment.

Polycystic Ovary Syndrome (PCOS), a multifaceted endocrine disorder, affects a significant proportion of women globally, with its etiology rooted in both genetic and environmental factors. This study delves into the environmental aspect, particularly focusing on the role of endocrine-disrupting chemicals (EDCs) in the context of urbanization and industrialization. This research examines the impact of endocrine-disrupting chemicals (EDCs) - Bisphenol A (BPA), Mono-ethyl Hexyl Phthalate (MEHP), and Di-ethyl Hexyl Phthalate (DEHP) - on 40 women with Polycystic Ovary Syndrome (PCOS) across urban and rural Gujarat. Employing High-Performance Liquid Chromatography (HPLC) and chemiluminescence, we analyzed their blood samples for EDCs levels and hormonal parameters. Urban individuals displayed significantly higher BPA and DEHP concentrations, highlighting the environmental exposure differences. Notably, urban exposure to MEHP and DEHP correlated with a marked decrease in estradiol levels, while rural DEHP exposure was associated with an increase in estradiol but a decrease in prolactin and DHEAS levels. These findings illuminate the variable effects of EDC exposure on hormonal profiles in PCOS, influenced by geographical and environmental contexts. The study underscores the critical need for tailored environmental health policies to mitigate the diverse impacts of EDCs, advocating for a nuanced approach to PCOS management that considers environmental exposures. Our insights contribute to the understanding of PCOS's hormonal dynamics, emphasizing the significance of addressing EDC exposure in different settings.

Elaborate biologic approval process delays care of patients with moderate-to-severe asthma.

Background: mAbs (biologics) are indicated in patients with poorly controlled moderate-to-severe asthma. The process of prior authorization and administration of a biologic requires exceptional commitment from clinical teams. Objective: Our aim was to evaluate the process of approval and administration of biologics for asthma and determine the most common reasons associated with denials of biologics and delays in administration. Methods: We examined the records of patients with asthma who were prescribed biologics from January 2018 to January 2020 at 2 centers, Montefiore Medical Center (Bronx, NY) and Scripps Clinics (San Diego, Calif). Demographics, insurance information, and details on the approval process were collected. Results: After querying of electronic health records, the records of 352 and 70 patients with moderate-to-severe asthma were included from Montefiore and Scripps, respectively. Most patients at Montefiore (58.2%) were insured under Managed Care Medicaid (MC Medicaid), whereas most patients at Scripps (61.4%) had commercial insurance. The median times from prescription to administration of a biologic were similar: 34 days (interquartile range [IQR] = 18-63 days) and 34 days (IQR = 22.5-56.0 days) (P = .97) for Montefiore and Scripps, respectively. However, the median approval time for Montefiore was 6 days (IQR = 1-20 days) and that for Scripps was 22 days (IQR = 10-36 days) (P < .001). Approval times for prescriptions requiring appeals were significantly longer than for prescriptions approved after the initial submission: 23 days versus 2.5 days and 40.5 days versus 15.5 days (for Montefiore and Scripps, respectively [P < .001 for both]). Conclusions: Lengthy appeals contribute to delays between prescribing and administering a biologic. Site-specific practices and insurance coverage influence approval timing of the biologics for asthma.

Pegylated Liposomal Alendronate Biodistribution, Immune Modulation, and Tumor Growth Inhibition in a Murine Melanoma Model.

While tumor-associated macrophages (TAM) have pro-tumoral activity, the ablation of macrophages in cancer may be undesirable since they also have anti-tumoral functions, including T cell priming and activation against tumor antigens. Alendronate is a potent amino-bisphosphonate that modulates the function of macrophages in vitro, with potential as an immunotherapy if its low systemic bioavailability can be addressed. We repurposed alendronate in a non-leaky and long-circulating liposomal carrier similar to that of the clinically approved pegylated liposomal doxorubicin to facilitate rapid clinical translation. Here, we tested liposomal alendronate (PLA) as an immunotherapeutic agent for cancer in comparison with a standard of care immunotherapy, a PD-1 immune checkpoint inhibitor. We showed that the PLA induced bone marrow-derived murine non-activated macrophages and M2-macrophages to polarize towards an M1-functionality, as evidenced by gene expression, cytokine secretion, and lipidomic profiles. Free alendronate had negligible effects, indicating that liposome encapsulation is necessary for the modulation of macrophage activity. In vivo, the PLA showed significant accumulation in tumor and tumor-draining lymph nodes, sites of tumor immunosuppression that are targets of immunotherapy. The PLA remodeled the tumor microenvironment towards a less immunosuppressive milieu, as indicated by a decrease in TAM and helper T cells, and inhibited the growth of established tumors in the B16-OVA melanoma model. The improved bioavailability and the beneficial effects of PLA on macrophages suggest its potential application as immunotherapy that could synergize with T-cell-targeted therapies and chemotherapies to induce immunogenic cell death. PLA warrants further clinical development, and these clinical trials should incorporate tumor and blood biomarkers or immunophenotyping studies to verify the anti-immunosuppressive effect of PLA in humans.

Association of FTO gene variant rs9939609 with polycystic ovary syndrome from Gujarat, India.

BACKGROUND: Polycystic ovary syndrome is a multifactorial endocrine disorder impacting women of reproductive age. Variations within the FTO gene have been linked to both obesity and type 2 diabetes mellitus. Given that PCOS is frequently associated with obesity and compromised glucose tolerance, we investigated the prevalence of the rs9939609 variant within the FTO gene among women diagnosed with PCOS and a control group. Our aim is to uncover potential correlations between this genetic variant, metabolic attributes, and endocrine markers within the Gujarat province of India. METHOD: We enrolled a total of 114 participants, (62 individuals diagnosed with PCOS and 52 healthy controls). DNA extraction from venous blood was conducted for all participants. The rs9939609 polymorphism was investigated through tetra-primer amplification refractory mutation system-polymerase chain reaction. Furthermore, we performed biochemical assessments to quantify levels of estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), total testosterone, prolactin (PRL), and Dehydroepiandrosterone sulfate (DHEAS). Statistical analyses were carried out utilizing SPSS version 21 (IBM, USA). RESULTS: The present study did not reveal any noteworthy association between cases and controls. The frequencies of genotypes and alleles within the cohorts displayed no statistically significant differences (p = 0.25, p = 0.68, and p = 0.78, respectively). The dominant model indicated a modest risk (OR:1.13, 95%CI: 0.55 to 2.38) toward PCOS development. There was a noticeable statistical difference observed in the levels of total testosterone, DHEAS, and BMI between the case and control groups (p < 0.002, p < 0.0002, p < 0.0008). However, no variations in clinical variables were observed among genotypes within the PCOS group. CONCLUSION: This is the first study to investigate the association of FTO gene polymorphism and PCOS in Gujarati population. Our study findings indicate that the FTO gene variant is not directly linked to the onset of PCOS. However, it appears to exert an influence on metabolic factors such as obesity and insulin resistance. Notably, our results suggest that insulin resistance is more frequently observed among PCOS patients who are obese, as compared to those with non-obese PCOS patients.

Assessment of gut microbial ß-glucuronidase and ß-glucosidase activity in women with polycystic ovary syndrome.

PCOS is a prevalent endocrine disorder among women of reproductive age, characterized by hormonal imbalances and metabolic disturbances. This study explores the correlation between gut microbial ß-glucuronidase and ß-glucosidase and PCOS, focusing on their association with hormone levels and other clinical parameters. In this case-control study, fecal samples were collected from women of reproductive age, both with and without PCOS. The analysis of gut ß-glucuronidase and ß-glucosidase enzymes was conducted with the other clinical parameters, including body mass index, hormone levels, and hirsutism. These factors were then subjected to correlation analysis. PCOS women showed significantly higher levels of ß-glucuronidase activity with a statistically significant P-value (0.05 ± 0.1 vs. 0.04 ± 0.1; P = 0.006) as well as ß-glucosidase activity (0.13 ± 0.08 vs. 0.09 ± 0.05; P = 0.06) compared to the controls. This study also revealed intriguing connections between the selected enzymes and hormone levels, particularly testosterone and estradiol. Gut microbial enzymes ß-glucuronidase and ß-glucosidase may be used as biomarkers for early detection and monitoring of PCOS in women with metabolic challenges. It could lead to improved diagnostic tools and treatment options.

Penile ulcerative pyoderma gangrenosum: A rare entity.

Pyoderma gangrenosum (PG) is a rare, chronic, ulcerative, neutrophilic, and inflammatory skin disease. It most commonly affects the lower limb, may affect peristomal skin, and rarely involves mucosal and internal sites. Genital involvement has been rarely reported. Hereby, we report a case of penile PG in a 70-year-old male treated with oral steroids.

Interventions Increase Vaccination Rates in Inflammatory Bowel Disease and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with immune-mediated conditions such as IBD and RA are at risk for vaccine-preventable infections. Despite guideline recommendations, prior studies have shown suboptimal vaccination rates. AIM: We conducted a systematic review and meta-analysis to compare the different interventions intended to increase vaccination rates. METHODS: A systematic search was conducted of MEDLINE/PubMed, Embase, CINAHL, and Cochrane Library up to 2020 for studies with interventions intended to increase vaccination rates. We performed a random-effects meta-analysis to generate pooled odds ratios (ORs) to assess all interventions against no interventions. Our primary outcome was pneumococcal vaccination (PCV) rate. RESULTS: Our review found 8580 articles, for which 15 IBD and 8 RA articles met the inclusion criteria; 21 articles were included in the analysis. PCV was the predominant vaccination (91%). In our analysis of patients with IBD, almost all interventions (patient-oriented, physician-oriented, or barrier-oriented) increased PCV uptake [OR, 4.74; 95% CI, 2.44-6.56, I2 = 90%] compared to no intervention. The greatest effect was seen in barrier-oriented studies [OR, 12.68; 95% CI, 2.21-72.62, I2 = 92%]. For RA data, all interventions had increased PCV uptake compared to no interventions (OR 2.74; 95% CI, 1.80-4.17, I2 = 95%). CONCLUSION: Our data suggest that many different interventions can increase PCV rates. It appears that barrier-oriented interventions may have the greatest positive effect on increasing PCV uptake. However, clinicians should be encouraged to implement measures best suited to their practice. Future high-quality randomized controlled trials are needed to determine the best approach to optimize vaccination rates.

Adverse Cutaneous Drug Reactions at a Rural-Based Tertiary Health-Care Center in Gujarat: An Eleven Year Study.

Background: An adverse cutaneous drug reaction (ACDR) is an undesirable change in structure and function of the skin, its appendages, or mucous membranes due to drugs. Aims and Objectives: To study the demographic details, clinical patterns, mucocutaneous involvement, causality, and the offending drugs causing ACDR. Materials and Methods: In this observational study, we have seen 2,96,544 patients in the skin department at a rural-based tertiary health-care hospital, out of which 728 cases were diagnosed to have ACDR from a time span of April 2010 to March 2021. The causality assessment system WHO-UMC (World Health Organization Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre), the Naranjo probability scale, and Hartwigs score were calculated for patients. Results: Out of 728 cases, males were 371 (50.96%); most common age group was 21-30 years (25.13%). The most common presenting complaint was erythematous rash (21.29%). Antimicrobials (n = 345, 47.39%) were the most common drug group. Most common mucosa involved was oral mucosa and most common pattern of reaction seen was maculopapular rash (25%) among these patients. In the causality assessment using WHO guidelines, there were 66 (9.1%) certain, 224 (30.83%) probable, and 436 (60%) possible cases. Naranjo score showed 73 (10%) definite cases, 255 (35%) probable cases, and 400 (55%) possible cases, while Hartwigs score showed level 2 in 122 (16.7%) cases and level 3 in 412 (56.7%) cases. Conclusion: Wide spectrum of drug reactions were observed in this study. Antimicrobials were the most common causative agents of ACDR.

Comparative effects of free doxorubicin, liposome encapsulated doxorubicin and liposome co-encapsulated alendronate and doxorubicin (PLAD) on the tumor immunologic milieu in a mouse fibrosarcoma model.

Background: We have previously shown that alendronate, an amino-bisphosphonate, when reformulated in liposomes, can significantly enhance the efficacy of cytotoxic chemotherapies and help remodel the immunosuppressive tumor microenvironment towards an immune-permissive milieu resulting in increased anticancer efficacy. In addition, we have previously shown that the strong metal-chelating properties of alendronate can be exploited for nuclear imaging of liposomal biodistribution. To further improve anticancer efficacy, a pegylated liposome formulation co-encapsulating alendronate and doxorubicin (PLAD) has been developed. In this study, we examined the effects of PLAD on the tumor immunologic milieu in a mouse fibrosarcoma model in which the tumor microenvironment is heavily infiltrated with tumor-associated macrophages (TAM) that are associated with poor prognosis and treatment resistance. Methods: Doxorubicin biodistribution, characterization of the tumor immunologic milieu, cellular doxorubicin uptake, and tumor growth studies were performed in Balb/c mice bearing subcutaneously implanted WEHI-164 fibrosarcoma cells treated intravenously with PLAD, pegylated liposomal doxorubicin (PLD), free doxorubicin, or vehicle. Results: PLAD delivery resulted in a high level of tumor doxorubicin that was 20 to 30-fold greater than in free doxorubicin treated mice, and non-significantly higher than in PLD treated mice. PLAD also resulted in increased uptake in spleen and slightly lower plasma levels as compared to PLD. Importantly, our results showed that PLAD, and to a lesser extent PLD, shifted cellular drug uptake to TAM and to monocytic myeloid-derived suppressor cells (MDSC), while there was no drug uptake in neutrophilic MDSC or lymphoid cells. Free doxorubicin cellular drug uptake was below detectable levels. PLAD, and to a lesser extent PLD, also induced significant changes in number and functionality of tumor-infiltrating TAM, MDSC, Treg, NKT, and NK cells that are consistent with enhanced antitumor immune responses in the tumor microenvironment. In contrast, free doxorubicin induced moderate changes in the tumor microenvironment that could promote (decreased Treg) or be detrimental to antitumor immune responses (decreased M1 TAM and NK cells). These immune modulatory effects are reflected in the therapeutic study which showed that PLAD and PLD inhibited tumor growth and significantly prolonged survival, while free doxorubicin showed little or no anticancer activity. Conclusion: We show that liposomal delivery of doxorubicin not only alters pharmacokinetics, but also dramatically changes the immune modulatory activity of the drug cargo. In addition, our data support that the PLAD nanotheranostic platform further enhances some immune changes that may act in synergy with its cytotoxic chemotherapy effects.

Interprofessional learning for dental and pharmacy professionals: learning together changes how you work together.

Can an interprofessionally designed and facilitated learning event change the way professionals understand each other's roles, enable them to better work with each other and improve patient care? Pharmacy and dental professionals are contractors to the NHS, providing services to the public. The way both professions are funded encourages them to generally work in isolation from the wider NHS, in contrast to other areas of healthcare and NHS systems. This study explores how working collaboratively at all stages of design, development, facilitation and engagement of a learning event impacts on the professionals taking part. It also explores how learning interprofessionally can change the way dental and pharmacy professionals work together, suggesting this way of learning is beneficial to improving working relationships between the sectors.The study explored the ways that shared learning between professions could be approached and encouraged. Pharmacy professionals expressed that they felt more informed and confident giving dental advice to patients. Dental professionals recognised that pharmacy professionals could help support and manage patients. All professionals could see the importance of multidisciplinary working to improve understanding of the other professionals' role. The workshops showed that shared learning is an important aspect to help engage and integrate healthcare systems.

A Case of Systemic AL Amyloidosis Diagnosed by Screening Colonoscopy.

Amyloidosis encompasses several diseases associated with deposition of low-molecular-weight proteins in an abnormal configuration. In light-chain amyloidosis (AL), monoclonal free lambda (λ) or kappa (κ) light chains are the amyloid proteins involved and can deposit in almost any organ. Symptoms vary depending on presence and extent of organ involvement, and thus, clinical presentation varies. Diagnosis requires biopsy of the affected tissue, and sometimes, fat pad or bone marrow biopsy is completed initially. Prognosis of AL amyloidosis depends on the presence of cardiac involvement. Treatment of AL amyloidosis involves systemic chemotherapy and evaluation for autologous stem cell transplant. Herein, we present a case report of an asymptomatic middle-aged female who was diagnosed with AL amyloidosis during an average-risk screening colonoscopy, which is an unusual setting. We discuss the workup involved, clinical presentation, and gastroenterology-related organ involvement.

Metastatic Renal Cell Carcinoma Presenting as Gastrointestinal Bleeding.

Approximately 85% of kidney tumors are renal cell carcinoma (RCC). RCC commonly metastasizes to the lung, bone, and lymph nodes; however, gastric metastasis is exceedingly rare. We present an 86-year-old woman with left-sided RCC with known metastatic disease to the lungs, lymph nodes, and bone, who presented with acute blood loss anemia. After hemodynamic stabilization, esophagogastroduodenoscopy revealed a large infiltrative, polypoid, and ulcerated polyp in the gastric body. After complete polypectomy, histological examination demonstrated gastric mucosa ulcerated by clear-cell carcinoma, compatible with metastatic RCC. Our patient was successfully treated with palliative radiation to the gastric body.

The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis.

Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women's lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.

Physicochemical Stability and Compatibility of Revefenacin (LAMA) and Formoterol Fumarate (LABA) Inhalation Solution Admixture.

Revefenacin inhalation solution, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate inhalation solution, a long-acting ß-agonist (LABA), are indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease. LAMA or LABA monotherapy, or a combination of LAMA/LABA for more severe symptoms, is recommended as first-line treatment in this patient population. We conducted a study to test the physicochemical properties of revefenacin and formoterol fumarate inhalation solution admixture in support of a clinical trial evaluating the safety of these nebulized bronchodilators, administered in sequence, and as a combination, in patients with chronic obstructive pulmonary disease (NCT03573817). The admixture of these two products was evaluated for changes in appearance, pH, osmolality, active drug content, purity, and impurity/degradant levels at 25°C for up to 25 hours. No substantial changes were observed in the physicochemical properties of revefenacin inhalation solution and formoterol fumarate inhalation solution admixture, demonstrating the physicochemical compatibility and stability of the two drugs in solution for up to 25 hours at room temperature.

Application of 32 Full Factorial Design and Desirability Function for Optimizing The Manufacturing Process for Directly Compressible Multi-Functional Co-Processed Excipient.

BACKGROUND: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. OBJECTIVE: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. METHODS: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr's index, Hausner's ratio, tensile strength and Kuno's constant were selected as response variables. RESULT: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. CONCLUSION: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.

Therapeutic Targeting of Vasculature in the Premetastatic and Metastatic Niches Reduces Lung Metastasis.

In the metastasis-targeted organs, angiogenesis is essential for the progression of dormant micrometastases to rapidly growing and clinically overt lesions. However, we observed changes suggesting angiogenic switching in the mouse lungs prior to arrival of tumor cells (i.e., in the premetastatic niche) in the models of breast carcinoma. This angiogenic switching appears to be caused by myeloid-derived suppressor cells recruited to the premetastatic lungs through complement C5a receptor 1 signaling. These myeloid cells are known to secrete several proangiogenic factors in tumors, including IL-1ß and matrix metalloproteinase-9, and we found upregulation of these genes in the premetastatic lungs. Blockade of C5a receptor 1 synergized with antiangiogenic Listeria monocytogenes-based vaccines to decrease the lung metastatic burden by reducing vascular density and improving antitumor immunity in the lungs. This was mediated even when growth of primary breast tumors was not affected by these treatments. This work provides initial evidence that angiogenesis contributes to the premetastatic niche in rapidly progressing cancers and that inhibiting this process through immunotherapy is beneficial for reducing or even preventing metastasis.