This study sought to determine the relationship between cervical cancer recurrence and post-treatment change in standardized uptake value (SUV) of 18F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in the cervix and lymph nodes. This retrospective cohort study included patients who received curative intent radiation therapy for biopsy-proven stage I–IVA locally advanced cervical cancer at a single tertiary referral center from 2009 to 2021. The exposure was percent change in SUV from pre- to post-treatment FDG-PET scans at the cervix and lymph nodes. The primary outcome was recurrence rate, and secondary outcomes were overall and progression-free survival. Firth’s penalized logistic regression and Cox proportional hazards models were used to assess associations. 55 patients met eligibility criteria. Recurrence rate was 27

BACKGROUND:Breast cancer survivors (BCS) demonstrate attenuated immune cell mobilization following acute exercise, with partial restoration following exercise training. Epinephrine (EPI) and norepinephrine (NE) are responsive to exercise-stress and directly regulate immune cell function, indicating a potential role in this restorative process. Similar attenuations in catecholaminergic signaling have been reported in BCS post-exercise; however, it is unknown whether this is maintained within a trained state. We hypothesized that compared to non-cancer controls (CON), acute exercise would induce an attenuated catecholaminergic response in untrained BCS, which would be recovered to levels similar to CON after training. AIM:To compare acute exercise-induced catecholaminergic responses between BCS and CON before (PRE) and after (POST) completing a community-based exercise intervention. METHODS:Thirteen BCS (age: 56 ± 2 years, body fat: 39.7% ± 1.3%) and 13 CON (age: 56 ± 2 years, body fat: 41.2% ± 1.7%) performed 45 minutes of intermittent cycling at 60% peak power output PRE and POST 16 weeks of community-based exercise training. Blood samples were collected at baseline (BASE), immediately (0 hour), and 1-hour (1 hour) post-exercise for assessment of the acute EPI and NE response. Separate linear mixed models were used for PRE and POST EPI and NE assessment. RESULTS:At PRE, both BCS and CON demonstrated increases in EPI (+87.4 pg∙mL-1, P < 0.001) and NE (+1295 pg∙mL-1, P < 0.001) at 0 hour, with no group differences. At POST, group differences in NE initiation (0 hour-BASE) were not statistically significant (-544.9 pg∙mL-1, P = 0.115, g = 0.92), despite divergent responses between BCS (+28%, P = 0.175, g = 0.36) and CON (-13%, P = 0.377, g = 0.23). No group differences were observed for NE recovery (1 hour-0 hour) nor for EPI initiation or recovery. CONCLUSION:BCS and CON present with similar exercise-induced catecholaminergic responses regardless of training, suggesting an alternative mechanism may have made a greater contribution to the training-induced immune cell revival previously observed.

OBJECTIVES:The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS:A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS:Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS:Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.

The addition of IV triapine to chemoradiation appeared active in phase I and II studies but drug delivery is cumbersome. We examined PO triapine with cisplatin chemoradiation. We implemented a 3 + 3 design for PO triapine dose escalation with expansion, starting at 100 mg, five days a week for five weeks while receiving radiation with weekly IV cisplatin for locally advanced cervical or vaginal cancer. Maximum tolerated dose (MTD), dose limiting toxicity (DLT), adverse events, pharmacokinetics (PK), pharmacodynamics (PD), and metabolic complete response (mCR) were assessed. 19/21 patients were DLT evaluable. DLTs included grade 4 neutropenia (n = 2), leukopenia (n = 2), lymphopenia (n = 2), and hypokalemia (n = 1). Grade 3 toxicities at least possibly related were as expected for cisplatin chemoradiation: lymphopenia (n = 12), anemia (n = 10), neutropenia (n = 4), leukopenia (n = 8), decreased platelets (n = 2), hypertension (n = 1), and hyponatremia (n = 1). MTD and RP2D were established at 100 mg. 8/13 evaluable patients had a mCR. Triapine had a bioavailability of 59

IntroductionEndometrial cancer is the most common malignancy of the female reproductive system in the United States. Asparagus officinalis is a versatile, nutrient-dense, low-calorie vegetable that contains various bioactive metabolites that have shown a variety of biologic functions beneficial to health. The metabolites from asparagus officinalis extracts or asparagus officinalis extracts exhibit significant anti-tumorigenic activity in some pre-clinical models of cancer.MethodsEndometrial cancer cells were used to study the effects of asparagus officinalis on anti-proliferation, anti-invasion and increased sensitivity to cisplatin, and obese and lean Lkb1fl/flp53fl/fl mouse model of endometrial cancer was used to study the role of asparagus officinalis in tumor growth.ResultsTreatment with increasing concentrations of Asparagus officinalis extracts significantly inhibited cell proliferation, reduced glycolytic activity, induced cellular stress and apoptosis, caused cell cycle G1 arrest, increased the sensitivity of cells to cisplatin, reduced cell adhesion and invasion, and activation of AMPK and inhibition of the AKT/mTOR and MAPK signaling pathways in endometrial cancer cells. Moreover, asparagus officinalis extracts suppressed cell adhesion and invasion through the modulation of the epithelial-to-mesenchymal transition process. Asparagus officinalis extract treatment for 4 weeks resulted in a significant reduction in tumor growth in Lkb1fl/flp53fl/fl mice under both obese and lean conditions, with a decrease in Ki-67 and vascular endothelial growth factor expression and an increase in Bip expression in endometrial tumors.DiscussionThese findings provide strong preclinical evidence for the potential therapeutic benefit of asparagus officinalis extract as a novel dietary strategy in the treatment of endometrial cancer. Further clinical trials of dietary intervention of asparagus officinalis or combination with cisplatin in patients with endometrial cancer are warranted.

•Metastatic disease to the small bowel may present with intussusception.•Clinical decision making for malignant bowel obstruction is difficult and individual specific.•Malignant bowel obstruction due to metastatic year has an average life expectancy of less than 200 days.

Objective: Cervical cancer is a highly preventable malignancy caused by HPV that begins with the development of precancerous lesions (high risk cervical intraepithelial neoplasia grades 2 or 3 - hrCIN). As cancer is a metabolic disease, individuals with metabolic conditions such as diabetes, high cholesterol (hcho) and high blood pressure (hbp) may be at higher risk of developing hrCIN. Given the higher prevalence among Black women, we sought to determine whether these metabolic conditions increase the risk of hrCIN differentially by race. Methods: We used data from hospital and physician billing claims for any CIN diagnosis occurring at the Virginia Commonwealth University Health System (VCUHS) from 01/01/2014 through 12/04/2021, along with respective clinical and sociodemographic characteristics at the time of diagnosis. We estimated the risk of high-grade dysplasia (CIN2+ versus CIN1) among women with various metabolic diseases, using logistic regression (LR) with a backward selection approach (removing terms with p ≥ 0.2 and adding those with p < 0.1) to identify most relevant confounding factors. Results: There were 2,761 women diagnosed with CIN 1, 2, 3, and unspecified dysplasia of the cervix uteri with respective prevalence of 30%, 45%, 11%, and 14%. The prevalence of hrCIN did not vary by race (48% versus 52% for non-Latina (nL)-whites versus nL-Blacks respectively). Of the variables included in the LR model (age, marital status, religion, preferred language, insurance status, Body Mass Index, HIV, HPV, presence of bacterial vaginosis, hypertension, cholesterol, diabetes, pulmonary conditions, arthritis, heart conditions, pregnancy status, parity, smoking, alcohol, and previous cancer diagnoses), only pregnancy status, diabetes, hypertension, cholesterol, insurance, language, pulmonary conditions, and HPV remained in the final LR model. We identified an interaction between hypertension and cholesterol (p=0.03) where the odds of a hrCIN among women with both, hypertension, and cholesterol, were more than twice compared to women with neither comorbidity (OR=2.2, 95%CI: 1.1, 4.3). Stratified by race, the elevated risk of hrCIN was only significant among nL-Black women (p=0.05, OR=2.9, 95%CI: 1.1, 8.6). Conclusions: Despite no apparent difference in the incidence of hrCIN by race in this dataset, our analysis revealed an excess risk of hrCIN that was only present for Black women with both hypertension and hypercholesterolemia. These comorbidities are both overrepresented in nL-Blacks and are associated with low grade systemic inflammation, which may promote HPV persistence and progression to hrCIN. If replicable, this association deserves further investigation to assess its biological underpinnings and potential as a point of intervention to reduce the risk of CIN progression and cervical cancer. Citation Format: Shreya R. Raman, Stephanie A. Sullivan, Robert A. Winn, Katherine Y. Tossas. "Am I at risk for cervical cancer?": Racial disparity implications of an unexpected relationship between chronic conditions and precancerous lesions [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C098.

PURPOSE:Endometrial Cancer (EC) is the most common gynecologic malignancy in the United States. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk. Treatment can cause significant vaginal changes, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These are not life threatening, but affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are inconsistent recommendations on use. This prospective study compared vaginal length changes and sexual function in women compliant with dilation versus not after surgery and RT. METHODS AND MATERIALS:Enrolled patients underwent surgery for Stage I-IIIC EC ±RT. Vaginal dilator use was recommended for women receiving RT (external beam or brachytherapy). Vaginal length was measured with a vaginal sound and the Female Sexual Function Index (FSFI) was used to assess sexual function. RESULTS:Forty-one enrolled patients had sufficient data for analysis. Dilation significantly increased FSFI scores (p = 0.02) while RT without dilation showed a significant decrease (p = 0.04). Dilation helped maintain vaginal length for all patients (0 cm vs. 1.8 cm loss (p = 0.03)). Individual arms did not show statistically significant changes in length with dilation, though the trend showed RT without dilation had an average loss of 2.3 cm as compared to only 0.2 cm for regular dilation. Notably, there was no difference in length change with dilation for surgery alone versus surgery and RT (p = 0.14). CONCLUSION:This data provides novel, prospective evidence of the benefit of vaginal dilation for maintaining vaginal length and improving sexual health after any pelvic treatment for EC. This evidence also supports that the addition of RT after surgery does not appear to significantly worsen vaginal shortening. This study has important implications for providing a strong foundation for future studies and helping to establish solid clinical management criteria for the prevention of vaginal stenosis and promotion of female sexual health.

Objective: This study sought to determine if patients with early stage cervical cancer who possessed intermediate-high risk factors (defined by Peters or Sedlis criteria) and had pathologically negative lymph nodes at the time of surgery had higher rates of low volume metastases (LVM) on retrospective ultrastaging. Methods: This IRB-approved retrospective cohort study collected data via chart review on early stage, surgically-treated node-negative cervical cancer patients who underwent postoperative adjuvant therapy, treated at a single institution from January 2011 through June 2021. Nodal blocks were retrospectively ultrastaged per standard protocol. Descriptive statistics were performed for analysis. Results: Over the 10-year study period, n = 20 patients met study inclusion criteria. Most patients were white with squamous cell histology, with a mean number of 25.15 (SD = 12) nodes examined on initial pathologic evaluation. 85 % (n = 17) patients were pathologic stage IB. 85 % of the cohort were recommended for adjuvant radiation, with the remaining 15 % for cisplatin-based chemoradiation. LVM in the form of micrometastasis was retrospectively identified in one patient (5 %) who had received whole pelvic radiation and recurred locally within the irradiated field. Conclusions: This small retrospective series of surgically managed cervical cancer with intermediate-high risk tumor factors identified only 1 patient with LVM, representing 5% of the total population. The biologic importance of ITC and LVM remains unclear in cervical cancer, however this investigation highlights the low incidence even when all nodes are evaluated in a higher risk cohort. The presence of LVM would not have changed management decisions based on this retrospective analysis.

Introduction Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme involved in the repair of DNA single-strand breaks (SSB). The recent development of poly(ADP-ribose) polymerase inhibitors (PARPi) results from over 45 years of studies. When the activity of PARP1 or PARP2 is compromised, DNA SSB lesions are unresolved and can be converted to DNA double-strand breaks (DSBs) by the cellular transcription mechanisms. ARID1A (also called BAF250a) is an important component of the mammalian Switch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex. ARID1A gene demonstrates >50% of mutation rate in ovarian clear-cell carcinomas (OCCC). Mutated or downregulated ARID1A significantly compromises the Homologous Recombination Repair (HRR) of DNA DSB. Results The present study demonstrated that downregulated or mutated ARID1A attenuates DNA HRR through stimulation of the PI3K/Akt1 pathway and makes tumor cells highly sensitive to PARPi and PARPi/ionizing radiation (IR) combination. We showed that PI3K/Akt1 pathway plays an important role in the sensitization of cancer cell lines with compromised function of ARID1A to PARPi treatment. Discussion We believe that using of PARPi monotherapy or in combination with radiation therapy is an appealing strategy for treating ARID1A-mutated cancers, as well as many other types of PI3K/Akt1-driven cancers.

This case report describes a unique pattern of human epidermal growth factor receptor 2 expression in a patient with uterine carcinosarcoma. The endometrial tumor showed biphasic morphology composed of serous carcinoma and a heterologous high-grade sarcoma component. Human epidermal growth factor receptor 2 immunostaining showed positive (3 + ) expression in foci of myoinvasion, lymphovascular invasion, and lymph node metastasis but was negative in both the endometrial surface tumor and sarcomatous component. Fluorescent in situ hybridization testing for human epidermal growth factor receptor 2 confirmed no amplification within the endometrial surface carcinoma component and amplification of the lymphovascular invasion component. As the use of human epidermal growth factor receptor 2 immunohistochemical evaluation becomes more commonplace for therapeutic consideration in patients with uterine carcinosarcoma, interpretation of the immunohistochemical should be performed preferentially on large tissue sections including both a surface, myoinvasive portions, and suspected areas of lymphovascular invasion and lymph node metastasis.

Objectives: High-grade squamous lesions of the cervix, (Cervical Intraepithelial Neoplasia (CIN) grade 2 and 3), are concerning, common, and costly precancerous findings, particularly for safety net hospitals who provide healthcare regardless of finances or insurance status. Epidemiologic surveillance of these lesions is uncommon but might be useful to guide preventive interventions. We sought to estimate the prevalence of CIN 2/3 and its racial and ethnic distribution, accounting for patient’s clinical and sociodemographic characteristics. Methods: We used data from hospital and physician billing claims for any CIN diagnosis occurring at the Virginia Commonwealth University Health System (VCUHS) from 01/01/2016 through 12/31/2020, along with respective clinical and sociodemographic characteristics at the time of diagnosis. We estimated average adjusted prevalence of CIN 2/3 lesions by race and ethnicity, from average marginal effects, after selecting most relevant patient factors from a logistic regression (LR) using backward selection (removing terms with p ≥ 0.2 and adding those with p < 0.1). Results: There were 1,538 women diagnosed with CIN 1, 2, 3, and unspecified dysplasia of the cervix uteri with respective prevalence of 45%, 14%, 12%, and 30%. CIN2/3 prevalence (26%) varied by race and ethnicity: Asians (39%) > Latinas (32%) > Whites (28%) >Blacks (23%) > Other (20%). Of the variables included in the LR model (age, marital status, religion, preferred language, insurance status, Body Mass Index, HIV, HPV, presence of bacterial vaginosis, hypertension, cholesterol, diabetes, pulmonary conditions, arthritis, heart conditions, pregnancy status, parity, smoking, alcohol, and previous cancer diagnoses), only age, diabetes, pulmonary conditions, smoking, and heart disease remained in the final LR model. The estimated average adjusted prevalence of a CIN 2/3 diagnosis remained highest for Asian women (35%, 95%CI: 17-52%), followed by Latinx (28%, 95%CI: 19-37%), Whites (25%, 95%CI 22-29%), Blacks (23%, 95%CI: 20-27%), and other (18%, 95%CI: 9-26%). Conclusions: The higher CIN 2/3 prevalence estimates among Asian women relative to other races and ethnicities is unexpected, as it does not align with current distribution of cervical cancer diagnoses at VCUHS (only 3% Asian), nor with the patterns of cervical cancer incidence and mortality rates in Virginia and in the United States, where Asian women have the lowest incidence and mortality. However, it potentially suggests a higher rate of regression, a finding supported by at least one surveillance study with similar findings. Citation Format: Shreya R. Raman, Stephanie A. Sullivan, Katherine Y. Tossas. Unexpected pattern in estimated prevalence of precancerous cervical lesions at a safety net hospital in Virginia: A case for epidemiologic surveillance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2208.

PURPOSE:GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS:Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS:Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time (P < .001) for all three groups. A group by time interaction (P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION:Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.

SPR965 is an inhibitor of PI3K and mTOR C1/C2 and has demonstrated anti-tumorigenic activity in a variety of solid tumors. We sought to determine the effects of SPR965 on cell proliferation and tumor growth in human serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer (KpB model) and identify the underlying mechanisms by which SPR965 inhibits cell and tumor growth. SPR965 showed marked anti-proliferative activity by causing cell cycle arrest and inducing cellular stress in ovarian cancer cells. Treatment with SPR965 significantly inhibited tumor growth in KpB mice, accompanied by downregulation of Ki67 and VEGF and upregulation of Bip expression in ovarian tumors. SPR965 also inhibited adhesion and invasion through induction of the epithelial–mesenchymal transition process. As expected, downregulation of phosphorylation of AKT and S6 was observed in SPR965-treated ovarian cancer cells and tumors. Our results suggest that SPR965 has significant anti-tumorigenic effects in serous ovarian cancer in vitro and in vivo. Thus, SPR965 should be evaluated as a promising targeted agent in future clinical trials of ovarian cancer.

Background Lipomatous tumors of the vulva are exceedingly rare, particularly in adolescents. We describe the work-up and management of an adolescent girl who presented with a large, well-vascularized vulvar mass. Case A 14-year-old girl presented with a large vulvar mass of unclear etiology. Magnetic resonance imaging of this mass revealed an ill-defined, well-vascularized mass with fat signal characteristics suggestive of a lipomatous tumor that was concerning for malignancy. We performed complete resection of the mass, and histologic evaluation revealed a vulvar hibernoma. There have been no signs of recurrence 1 year later. Summary and Conclusion Although rare, a hibernoma of the vulvar region may present in adolescence and may be concerning for malignancy on imaging. Complete resection of these tumors is recommended for definitive diagnosis and treatment.

Purpose: Over 65,000 women were diagnosed with endometrial cancer (EC) in 2020. Standard treatment is TAH/BSO with radiation therapy (RT) and chemotherapy given based on risk factors. These can cause significant changes in the vagina, including shortening, narrowing, loss of elasticity, atrophy, and dryness. These complications are not life threatening, but can affect a woman's physical, psychological, and social functioning. Adjuvant vaginal dilator use is often advised, but there are currently inconsistent recommendations on use and no prospective data to support its efficacy. This prospective study aimed to compare the change in vaginal length from baseline in women who are compliant with dilator use versus not after surgery and RT for EC, as well as potential effects on sexual function.

BACKGROUND Evidence for exercise as an efficacious strategy to improve aerobic capacity of breast cancer survivors (BCS) has come largely from intervention studies conducted in laboratory settings. There is an increasing need to translate to community-type settings, but the efficacy of those interventions using gold standard evaluation is not well-established. AIM To investigate whether similar improvement in aerobic capacity (maximal oxygen consumption [VO2]) measured with gold standard testing can be achieved through a community-based setting in BCS. METHODS A peak cardiopulmonary exercise test (VO2peak), 6-min walk test (6MWT), and timed up and go test (TUG) were assessed pre- and post-16 wk of progressive intensity aerobic and strength training exercise at a community center. RESULTS The sample consisted of 31 early BCS (< 1 year since treatment completion) and 15 controls (CTLs). Both groups significantly improved VO2peak (+1.2 mL/kg/min; P = 0.030), 6MWT (+35 meters; P < 0.001), and TUG (-0.44 s; P < 0.01) following training. Both groups improved peak cycling power during the cardiopulmonary exercise test with BCS improving by +10 watts more than the CTLs (P = 0.020). Average exercise attendance was 71% (34 of 48 possible days), but compliant days averaged only 60% of total days for aerobic, and < 40% for strength in both groups. CONCLUSION Community-based exercise programs can be an effective strategy to improve aerobic capacity and physical function for early-stage BCS but potentially not to the same extent observed in laboratory-based randomized controlled trials. Further research is needed to explore barriers and facilitators of exercise engagement in community-based centers to maximize training benefits for adults with cancer.

Ovarian cancer is one of the leading causes of female cancer death. Emerging evidence suggests that many dietary natural products have anti-tumorigenic activity, including that of asparagus officinalis. The current study aimed to assess the anti-tumorigenic and anti-metastatic effects of asparagus officinalis on serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer. Asparagus officinalis decreased cellular viability, caused cell cycle G1 phase arrest and induced apoptosis in the OVCAR5 and SKOV3 cells. Induction of apoptosis and inhibition of cell proliferation was rescued by the pan-caspase inhibitor, Z-VAD-FMK, implying that its cytotoxic effects were mainly dependent on caspase pathways. Asparagus officinalis increased levels of ROS and decreased mitochondrial membrane potential with corresponding increases in PERK, Bip, Calnexin PDI and ATF4 in both cell lines. Treatment with asparagus officinalis also reduced ability of adhesion and invasion through epithelial–mesenchymal transition and reduction of VEGF expression. The combination of Asparagus officinalis with paclitaxel had synergistic anti-proliferative activity. Furthermore, Asparagus officinalis significantly inhibited tumor growth and reduced serum VEGF in a genetically engineered mouse model of ovarian cancer under obese and lean conditions, accompanied with a decrease in the expression of Ki67, VEGF and phosphorylated S6, and in an increase in phosphorylation of AMPK in the ovarian tumor tissues. Overall, our data provide a pre-clinical rationale for asparagus officinalis in the prevention and treatment of ovarian cancer as a novel natural product.

Objectives: Lymph node (LN) metastasis and genomic profiles are important prognostic factors in endometrial cancer (EMCA). However, the prognostic significance of low volume metastasis found in sentinel lymph nodes (SLN) is unknown. We sought to determine if genomic mutations were associated with metastatic volume. Methods: Surgically staged women with EC who were enrolled in both a SLN clinical trial and tumor sequencing protocol were eligible. Relevant targets were enriched by a custom designed Agilent SureSelect hybrid capture enrichment library using standard protocols. Three specific gene mutations were evaluated, TP53, PTEN and PIK3CA in the primary tumor of patients with LN negative, LN positive and ITC disease. Results: 42 patients were eligible; of these, 7 (16.7%) had ITC only and 7 (16.7%) had micrometastatic or macrometastatic (LN positive) disease. No differences were seen in TP53, PIK3CA or PTEN between groups. All ITC patients with TP53 mutations were of non-endometrioid histology (2/7). Deeper myometrial invasion and lymph vascular space invasion were more likely to occur in the LN positive group (p < 0.01 for both). No patients with ITC had a recurrence in a median 67.7 months of follow-up since surgery. Conclusions: This pilot investigation did not identify differences between frequency of PIK3CA, PTEN or TP53 mutations in tumors and volume of LN metastasis. Low number of ITC limited the ability to detect genomic differences, however mutations appeared to align with expected histology. More work is needed to define the relationship between genomic mutations, histology, ITC, and prognosis.