Yuko Yamamura - Academia.edu (original) (raw)
Papers by Yuko Yamamura
Journal of Clinical Oncology, Feb 20, 2023
Scientific Reports, May 24, 2022
Journal of the advanced practitioner in oncology, Sep 1, 2022
Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and ... more Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic. Patients and Methods: We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics. Results: A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient; range 1–28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits; however, patients from 1.4% of visits were sent to the emergency center (EC) and/or admitted. Patients referred to the EC and/or admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1; p < .001). There were no associations between EC referral and gender, APP years of experience, or type of treatment. Conclusions: The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.
Nutrition and Cancer, 2000
Journal of Clinical Oncology, May 20, 2021
2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) w... more 2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of this study were to define the safety profile and to establish the recommended phase 2 dose (RP2D) of LVGN6051 alone or in combination with pembrolizumab. Pharmacokinetics, immunogenicity, pharmacodynamics and clinical efficacy will be also evaluated. Results: At the cut-off date on January 18, 2021, 16 subjects have been enrolled into the monotherapy cohorts (n=12, no DLT observed up to 7 mg/kg), and the combination cohort (n=4, ongoing at LVGN6051 2 mg/kg and pembrolizumab 200 mg, one DLT observed). No treatment-related adverse event (TRAE) was observed in monotherapy. Treatment-emergent adverse events (TEAE) in combination included increased ALT/AST, thrombocytopenia, and fatigue. In the combination cohort, one patient with predominant hepatic metastases and history of intermittent grade 2 hepatic impairment experienced grade 3 increased ALT/AST (DLT) on cycle 1 day 15 that were resolved to her baseline without corticosteroids on cycle 1 day 18. TRAE included increased ALT/AST, thrombocytopenia, neutropenia, nausea and fatigue. Seven of 10 evaluable patients in the monotherapy cohorts demonstrated stable disease with the longest treatment being 8+ months. Tumor reductions by >10% were observed in melanoma and neuroendocrine tumor on monotherapy. One patient with metastatic head and neck squamous cell carcinoma who had progressed on an anti-PD-L1 based therapy showed an immune partial response (iPR) for 6+ months to the combination therapy. Conclusions: Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed. While we continue assessing its safety profile, antitumor activity was observed in the LVGN6051 and pembrolizumab cohort. The favorable safety profile and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies. Clinical trial information: NCT04130542.
Journal of Clinical Oncology
TPS4605 Background: Complete response (CR) is still a rare event in patients with advanced clear ... more TPS4605 Background: Complete response (CR) is still a rare event in patients with advanced clear cell renal cell carcinoma (ccRCC). The combination of nivolumab plus cabozantinib was recently approved for the first-line treatment of ccRCC based on the CheckMate 9ER phase III study demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib. However, the CR rate was only 9%. Since the anti-tumor effects of immune checkpoint inhibitors are dependent on the presence of activated tumor-infiltrating T cells, drugs that could synergize with T cells’ anti-tumor activity can allow us to improve CR rates. Activation of the cGAS-STING pathway, the master regulator of anti-tumor immunity which is induced by radiation-induced DNA damage, is one promising mechanism that has been investigated. Many studies have shown that radiation treatment augments immune checkpoint inhibition. However, it is not always possible to radiate all metastatic l...
Journal of Clinical Oncology, 2021
2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) w... more 2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of ...
Cancer Research, 2021
Background: Wee1 kinase, which prevents premature mitotic entry by inhibiting cyclin-dependent ki... more Background: Wee1 kinase, which prevents premature mitotic entry by inhibiting cyclin-dependent kinases (CDKs), may be essential when cyclin E1 is overexpressed in order to prevent DNA damage and cell death. In preclinical studies, cancer models harboring CCNE1 amplification are highly sensitive to treatment with adavosertib, a Wee1 kinase inhibitor. A multicenter phase 2 study was conducted to assess the antitumor activity of adavosertib in patients with CCNE1 amplified advanced refractory solid tumors. Methods: Patients with advanced refractory solid tumors harboring CCNE1 amplification pre-identified in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory were eligible. They had refractory disease, on standard options available, or they declined standard-of-care therapy. Eligible patients must be aged ≥ 18 years and had measurable disease per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1, ECOG (Eastern Cooperative Oncology Group) performance status ...
Abstract: Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but t... more Abstract: Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various popula-tions has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluat-ing associations between risk and plasma levels of total carot-enoids, -cryptoxanthin, α- and trans-β-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of α-carotene, trans-β-carotene, β-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 wer...
Cancer Research, 2005
482 We have previously shown in a cohort of 526 prostate cancer (PC) patients treated with radica... more 482 We have previously shown in a cohort of 526 prostate cancer (PC) patients treated with radical prostatectomy (RP) that shorter androgen receptor CAG repeat lengths and obesity at diagnosis (BMI ≥ 30 kg/m2) are predictors of biochemical failure (BF) measured by rising PSA. We are now investigating the role that these factors along with other clinico-pathologic and demographic variables play in modulating time to progression. Our hypothesis is that earlier biochemical failure (≤36 months following RP) is associated with different factors than later increases in PSA (> 36 months). Using Cox proportional hazards models, we evaluated potential predictors of outcome with respect to time of BF (≤36 months vs. > 36 months post-RP) relative to men whose PC did not progress. We found that among patients with earlier BF (N = 63), age as a continuous variable (hazard ratio (HR) = 0.96, P = 0.03), obesity (HR = 1.78, P = 0.03) and clinico-pathological variables (e.g., lymph node involv...
Cancer Epidemiology, Biomarkers & Prevention, 2009
To date, little is known about the risk factors for the development of chronic myeloid leukemia (... more To date, little is known about the risk factors for the development of chronic myeloid leukemia (CML). Obesity, measured as body mass index, has been identified as a possible risk factor for several solid tumors as well as some adult hematopoietic malignancies. This case-control study (N = 253 cases and 270 controls), conducted at the University of Texas M. D. Anderson Cancer Center, investigated the role of obesity and adulthood weight gain in CML risk. Cases and controls were similar with respect to smoking, alcohol consumption, and occupational solvent and ionizing radiation exposure. Cases were significantly more likely to have a history of occupational exposure to agricultural chemicals (11% cases versus 3% controls, P = 0.001). Cases were more likely to be obese during adulthood compared with controls at age 25 [odds ratios (OR) = 4.29; 95% confidence intervals (95% CI), 1.63-11.3], at age 40 (OR = 5.12; 95% CI, 1.92-13.6), and at diagnosis (OR = 3.09; 95% CI, 1.56-6.13). Obes...
Cancer Epidemiology and Prevention Biomarkers, 2007
A40 Background: Little is known about racial/ethnic differences in prostate cancer (PCa) epidemio... more A40 Background: Little is known about racial/ethnic differences in prostate cancer (PCa) epidemiological risk factors. Some previous studies conducted in predominantly white populations have reported working in job with sedentary or light physical activity to be associated with increased PCa risk. This study evaluated the role of occupational physical activity as a possible explanation for disparate PCa risk in minority populations with known differences in risk. African-American men have the highest incidence rate in the world, whereas incidence in Hispanic men is slightly lower than in white men. Methods: This case-control study included 485 Texas men with PCa (176 of Mexican descent and 309 African-Americans) along with 481 age- and ethnicity-matched controls (174 of Mexican descent and 307 African-Americans). Demographic, lifetime occupational history, family history of cancer, lifestyle (e.g., smoking, alcohol, diet, and recreational physical activity) and anthropometric inform...
Cancer Research, 2015
Breast cancer (BrCa) is the most common invasive cancer in Hispanic women. Although at decreased ... more Breast cancer (BrCa) is the most common invasive cancer in Hispanic women. Although at decreased risk, Hispanic women are diagnosed at younger ages and with more aggressive disease than non-Hispanic Whites. Early detection is key in BrCa survival; however, there are no pre-diagnostic circulating biomarkers for early detection. This pilot nested case-control study based on our Mexican-American Cohort (MAC) study evaluates the role of global metabolic expression in predicting BrCa risk. MAC includes ∼23,000 participants in the Houston area with baseline blood specimens and epidemiological data. Using mass spectrometry-based global protein expression, 435 plasma metabolites were analyzed by Metabolon in 30 invasive BrCa cases (14 pre- (preM) and 16 post-menopausal (postM)) diagnosed 1-5 years after enrollment and 40 healthy controls (matched to cases on age, menopausal status) and length of follow-up). Mean age of preM women was 37.6 years (range 32-43) compared to 63.4 for postM (rang...
The Prostate, 2001
Although prostate cancer is the most common incident cancer in men, not much is known about its e... more Although prostate cancer is the most common incident cancer in men, not much is known about its etiology. We tested the hypothesis that expression levels of hMSH2 and hMLH1 in unaffected (normal) tissue play a role in the etiology of prostate cancer. Total RNA was extracted from peripheral blood lymphocytes of subjects ascertained by a case-control study (70 patients and 97 age- and ethnicity-matched controls). A multiplex reverse transcription-polymerase chain reaction assay was used to simultaneously evaluate the relative expression of hMSH2 and hMLH1, using beta-actin as the internal control. The relative gene expression levels of hMSH2 and hMLH1 were significantly lower in cases than in controls (P < 0.05 for both genes). When compared with the highest tertile of the controls, low expression levels (the middle and lowest tertiles) of hMLH1 were associated with significantly increased risk of prostate cancer in a dose-response relationship (ORs = 2.68, and 4.31; 95% confidence interval = 1.00-7.23 and 1.64-11.30, respectively) after adjustment for age, ethnicity, smoking status, and family history of prostate cancer. These results suggest that reduced expression of hMLH1 in peripheral lymphocytes may be a risk factor for prostate cancer. However, it cannot be ruled out that the reduced expression we observed may be caused by the disease status. Our findings and the factors that may affect the expression of hMLH1 need further confirmation in larger prospective studies.
The Prostate, 2008
BACKGROUND. There is a paucity of information regarding prostate cancer (PCa) risk factors among ... more BACKGROUND. There is a paucity of information regarding prostate cancer (PCa) risk factors among Hispanics, the fastest-growing ethnic group in the United States. METHODS. This population-based case-control study included 176 Texas men of Mexican descent with PCa and 174 age-and ethnicity-matched controls. Demographic, lifetime occupational history, family history of cancer, lifestyle (e.g., smoking, alcohol, diet, and recreational physical activity) and anthropometric information were collected by personal interviews. Chemical exposure and physical activity were determined using job-exposure matrices for each reported job. RESULTS. Logistic regression models adjusted for relevant covariates were used to evaluate their independent effects. Compared to controls, cases were three times more likely to work in jobs with high agrichemical exposure (OR ¼ 3.44, 95% CI 1.84-6.44), and 54% less likely to work in jobs with moderate/high occupational physical activity (OR ¼ 0.46, 95% CI 0.28-0.77). In analyses stratified by stage, cases with organ-confined PCa were three times more likely to have high agrichemical exposure (OR ¼ 3.39, 9%CI 1.68-6.84), and 56% less likely to have moderate/ high levels of occupational physical activity (OR ¼ 0.44, 95% CI 0.26-0.76). Increased risk of being diagnosed with advanced PCa was associated with obesity at time of diagnosis (OR ¼ 2.50, 95% CI 1.20-5.20) and high levels of agrichemical exposure (OR ¼ 4.65, 95% CI 1.97-10.97), but not with occupational physical activity. CONCLUSIONS. This case-control study, the first conducted in a homogeneous Hispanic population, identified modifiable PCa risk factors, such as physical activity and agrichemical exposure, which may be useful in developing interventions for this understudied population.
The Prostate, 2001
BACKGROUND. Higher prostate cancer mortality rates among US immigrants from countries with lower ... more BACKGROUND. Higher prostate cancer mortality rates among US immigrants from countries with lower rates suggest environmental in¯uences on prostate carcinogenesis (e.g., diet, body composition). METHODS. In a study identifying determinants of clinically relevant prostate cancer, we compared plasma concentrations of leptin, an adiposity-related hormone, in 48 men with tumors 0.5 cc measured after radical prostatectomy and 151 men with tumors b 0.5 cc in volume or with histologic evidence of extraprostatic extension but without metastases (``highvolume disease''), matched by age (AE 5 years) and year at diagnosis (AE 1 year). RESULTS. Men with high-volume disease exhibited higher leptin concentrations overall and after strati®cation by age, testosterone level, height, and body mass index (BMI). Analysis revealed that men with elevated leptin concentrations had an increased risk of diagnosis with high-volume disease (odds ratio (OR) 2.35, 95% con®dence interval (CI) 1.01±5.44), as did men with high leptin and high testosterone (OR 9.73, 95% CI 2.05±46.24) and men ! 5 H 8 HH with high leptin (OR 3.67, 95% CI 1.40±9.63). CONCLUSIONS. Leptin may affect the risk of clinically relevant prostate cancer through testosterone and factors related to stature and obesity.
Nutrition and Cancer, 1999
In the last several years, attention has been focused on comparing the Western diet, which is ric... more In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.
Nutrition and Cancer, 2005
Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relatio... more Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, b-cryptoxanthin, αand trans-β-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cislycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of α-carotene, trans-β-carotene, β-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-translycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of ≥7, n= 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of β-cryptoxanthin, α-carotene, trans-β-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression.
Journal of Clinical Oncology, Feb 20, 2023
Scientific Reports, May 24, 2022
Journal of the advanced practitioner in oncology, Sep 1, 2022
Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and ... more Background: Advanced practice providers (APPs) play important roles in enrolling, educating, and caring for patients in clinical trials. However, much remains unknown about the role of APPs in managing adverse events (AEs) in early (phase I to II) clinical trials. In this study, we assessed the outpatient management of grade 3 to 4 AEs by APPs in early trials and characterized the workflow of our APP Phase I to II Fast Track (FT) Clinic. Patients and Methods: We retrospectively reviewed records of patients with advanced or metastatic solid tumors enrolled in phase I to II clinical trials who were seen by APPs from September 2017 to August 2018 in the APP phase I to II FT clinic in the Department of Investigational Cancer Therapeutics. Results: A total of 808 patients enrolled in 159 clinical trials were seen in 2,697 visits (median 3 visits per patient; range 1–28) by 10 APPs. Treatment was interrupted in 6.9% of visits, and grade 3 to 4 AEs were seen in 5.4% of visits; however, patients from 1.4% of visits were sent to the emergency center (EC) and/or admitted. Patients referred to the EC and/or admitted were more likely to have baseline hypoalbuminemia, high lactate dehydrogenase, and poor Eastern Cooperative Oncology Group performance status (i.e., ECOG > 1; p < .001). There were no associations between EC referral and gender, APP years of experience, or type of treatment. Conclusions: The APP Phase I to II FT Clinic has an important role in the management of AEs by APPs in early clinical trials in the outpatient setting, potentially avoiding EC visits and admissions.
Nutrition and Cancer, 2000
Journal of Clinical Oncology, May 20, 2021
2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) w... more 2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of this study were to define the safety profile and to establish the recommended phase 2 dose (RP2D) of LVGN6051 alone or in combination with pembrolizumab. Pharmacokinetics, immunogenicity, pharmacodynamics and clinical efficacy will be also evaluated. Results: At the cut-off date on January 18, 2021, 16 subjects have been enrolled into the monotherapy cohorts (n=12, no DLT observed up to 7 mg/kg), and the combination cohort (n=4, ongoing at LVGN6051 2 mg/kg and pembrolizumab 200 mg, one DLT observed). No treatment-related adverse event (TRAE) was observed in monotherapy. Treatment-emergent adverse events (TEAE) in combination included increased ALT/AST, thrombocytopenia, and fatigue. In the combination cohort, one patient with predominant hepatic metastases and history of intermittent grade 2 hepatic impairment experienced grade 3 increased ALT/AST (DLT) on cycle 1 day 15 that were resolved to her baseline without corticosteroids on cycle 1 day 18. TRAE included increased ALT/AST, thrombocytopenia, neutropenia, nausea and fatigue. Seven of 10 evaluable patients in the monotherapy cohorts demonstrated stable disease with the longest treatment being 8+ months. Tumor reductions by >10% were observed in melanoma and neuroendocrine tumor on monotherapy. One patient with metastatic head and neck squamous cell carcinoma who had progressed on an anti-PD-L1 based therapy showed an immune partial response (iPR) for 6+ months to the combination therapy. Conclusions: Preliminary evidence showed that LVGN6051 was well tolerated and tumor shrinkages were observed. While we continue assessing its safety profile, antitumor activity was observed in the LVGN6051 and pembrolizumab cohort. The favorable safety profile and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies. Clinical trial information: NCT04130542.
Journal of Clinical Oncology
TPS4605 Background: Complete response (CR) is still a rare event in patients with advanced clear ... more TPS4605 Background: Complete response (CR) is still a rare event in patients with advanced clear cell renal cell carcinoma (ccRCC). The combination of nivolumab plus cabozantinib was recently approved for the first-line treatment of ccRCC based on the CheckMate 9ER phase III study demonstrating improved progression-free survival (PFS) and objective response rate (ORR) in comparison to sunitinib. However, the CR rate was only 9%. Since the anti-tumor effects of immune checkpoint inhibitors are dependent on the presence of activated tumor-infiltrating T cells, drugs that could synergize with T cells’ anti-tumor activity can allow us to improve CR rates. Activation of the cGAS-STING pathway, the master regulator of anti-tumor immunity which is induced by radiation-induced DNA damage, is one promising mechanism that has been investigated. Many studies have shown that radiation treatment augments immune checkpoint inhibition. However, it is not always possible to radiate all metastatic l...
Journal of Clinical Oncology, 2021
2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) w... more 2521 Background: LVGN6051, a monoclonal antibody against CD137 (also known as 4-1BB or TNFRSF9) with an engineered Fc capable of selectively binding to the Fcγ receptor IIB, acts as a conditional CD137 agonist, resulting in immune activation optimally in tumor microenvironment ( Qi, Nat. Commun. 2019 ). In preclinical models, LVGN6051 demonstrated robust anti-tumor efficacy and safety as a single agent and in combination with anti-PD-1 antibodies. Therefore, we have initiated this first-in-human study of LVGN6051 alone or in combination with pembrolizumab for the treatment of advanced or metastatic malignancy. Methods: This study includes accelerated dose escalation monotherapy up to 2 mg/kg of LVGN6051, and traditional 3 + 3 design for higher doses of LVGN6051 alone or in combination with pembrolizumab. Then, this study will enroll patients with specific types of malignancies following Simon’s two-stage design. Both agents are administered once every 3 weeks. Primary objectives of ...
Cancer Research, 2021
Background: Wee1 kinase, which prevents premature mitotic entry by inhibiting cyclin-dependent ki... more Background: Wee1 kinase, which prevents premature mitotic entry by inhibiting cyclin-dependent kinases (CDKs), may be essential when cyclin E1 is overexpressed in order to prevent DNA damage and cell death. In preclinical studies, cancer models harboring CCNE1 amplification are highly sensitive to treatment with adavosertib, a Wee1 kinase inhibitor. A multicenter phase 2 study was conducted to assess the antitumor activity of adavosertib in patients with CCNE1 amplified advanced refractory solid tumors. Methods: Patients with advanced refractory solid tumors harboring CCNE1 amplification pre-identified in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory were eligible. They had refractory disease, on standard options available, or they declined standard-of-care therapy. Eligible patients must be aged ≥ 18 years and had measurable disease per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1, ECOG (Eastern Cooperative Oncology Group) performance status ...
Abstract: Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but t... more Abstract: Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various popula-tions has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluat-ing associations between risk and plasma levels of total carot-enoids, -cryptoxanthin, α- and trans-β-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of α-carotene, trans-β-carotene, β-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 wer...
Cancer Research, 2005
482 We have previously shown in a cohort of 526 prostate cancer (PC) patients treated with radica... more 482 We have previously shown in a cohort of 526 prostate cancer (PC) patients treated with radical prostatectomy (RP) that shorter androgen receptor CAG repeat lengths and obesity at diagnosis (BMI ≥ 30 kg/m2) are predictors of biochemical failure (BF) measured by rising PSA. We are now investigating the role that these factors along with other clinico-pathologic and demographic variables play in modulating time to progression. Our hypothesis is that earlier biochemical failure (≤36 months following RP) is associated with different factors than later increases in PSA (> 36 months). Using Cox proportional hazards models, we evaluated potential predictors of outcome with respect to time of BF (≤36 months vs. > 36 months post-RP) relative to men whose PC did not progress. We found that among patients with earlier BF (N = 63), age as a continuous variable (hazard ratio (HR) = 0.96, P = 0.03), obesity (HR = 1.78, P = 0.03) and clinico-pathological variables (e.g., lymph node involv...
Cancer Epidemiology, Biomarkers & Prevention, 2009
To date, little is known about the risk factors for the development of chronic myeloid leukemia (... more To date, little is known about the risk factors for the development of chronic myeloid leukemia (CML). Obesity, measured as body mass index, has been identified as a possible risk factor for several solid tumors as well as some adult hematopoietic malignancies. This case-control study (N = 253 cases and 270 controls), conducted at the University of Texas M. D. Anderson Cancer Center, investigated the role of obesity and adulthood weight gain in CML risk. Cases and controls were similar with respect to smoking, alcohol consumption, and occupational solvent and ionizing radiation exposure. Cases were significantly more likely to have a history of occupational exposure to agricultural chemicals (11% cases versus 3% controls, P = 0.001). Cases were more likely to be obese during adulthood compared with controls at age 25 [odds ratios (OR) = 4.29; 95% confidence intervals (95% CI), 1.63-11.3], at age 40 (OR = 5.12; 95% CI, 1.92-13.6), and at diagnosis (OR = 3.09; 95% CI, 1.56-6.13). Obes...
Cancer Epidemiology and Prevention Biomarkers, 2007
A40 Background: Little is known about racial/ethnic differences in prostate cancer (PCa) epidemio... more A40 Background: Little is known about racial/ethnic differences in prostate cancer (PCa) epidemiological risk factors. Some previous studies conducted in predominantly white populations have reported working in job with sedentary or light physical activity to be associated with increased PCa risk. This study evaluated the role of occupational physical activity as a possible explanation for disparate PCa risk in minority populations with known differences in risk. African-American men have the highest incidence rate in the world, whereas incidence in Hispanic men is slightly lower than in white men. Methods: This case-control study included 485 Texas men with PCa (176 of Mexican descent and 309 African-Americans) along with 481 age- and ethnicity-matched controls (174 of Mexican descent and 307 African-Americans). Demographic, lifetime occupational history, family history of cancer, lifestyle (e.g., smoking, alcohol, diet, and recreational physical activity) and anthropometric inform...
Cancer Research, 2015
Breast cancer (BrCa) is the most common invasive cancer in Hispanic women. Although at decreased ... more Breast cancer (BrCa) is the most common invasive cancer in Hispanic women. Although at decreased risk, Hispanic women are diagnosed at younger ages and with more aggressive disease than non-Hispanic Whites. Early detection is key in BrCa survival; however, there are no pre-diagnostic circulating biomarkers for early detection. This pilot nested case-control study based on our Mexican-American Cohort (MAC) study evaluates the role of global metabolic expression in predicting BrCa risk. MAC includes ∼23,000 participants in the Houston area with baseline blood specimens and epidemiological data. Using mass spectrometry-based global protein expression, 435 plasma metabolites were analyzed by Metabolon in 30 invasive BrCa cases (14 pre- (preM) and 16 post-menopausal (postM)) diagnosed 1-5 years after enrollment and 40 healthy controls (matched to cases on age, menopausal status) and length of follow-up). Mean age of preM women was 37.6 years (range 32-43) compared to 63.4 for postM (rang...
The Prostate, 2001
Although prostate cancer is the most common incident cancer in men, not much is known about its e... more Although prostate cancer is the most common incident cancer in men, not much is known about its etiology. We tested the hypothesis that expression levels of hMSH2 and hMLH1 in unaffected (normal) tissue play a role in the etiology of prostate cancer. Total RNA was extracted from peripheral blood lymphocytes of subjects ascertained by a case-control study (70 patients and 97 age- and ethnicity-matched controls). A multiplex reverse transcription-polymerase chain reaction assay was used to simultaneously evaluate the relative expression of hMSH2 and hMLH1, using beta-actin as the internal control. The relative gene expression levels of hMSH2 and hMLH1 were significantly lower in cases than in controls (P < 0.05 for both genes). When compared with the highest tertile of the controls, low expression levels (the middle and lowest tertiles) of hMLH1 were associated with significantly increased risk of prostate cancer in a dose-response relationship (ORs = 2.68, and 4.31; 95% confidence interval = 1.00-7.23 and 1.64-11.30, respectively) after adjustment for age, ethnicity, smoking status, and family history of prostate cancer. These results suggest that reduced expression of hMLH1 in peripheral lymphocytes may be a risk factor for prostate cancer. However, it cannot be ruled out that the reduced expression we observed may be caused by the disease status. Our findings and the factors that may affect the expression of hMLH1 need further confirmation in larger prospective studies.
The Prostate, 2008
BACKGROUND. There is a paucity of information regarding prostate cancer (PCa) risk factors among ... more BACKGROUND. There is a paucity of information regarding prostate cancer (PCa) risk factors among Hispanics, the fastest-growing ethnic group in the United States. METHODS. This population-based case-control study included 176 Texas men of Mexican descent with PCa and 174 age-and ethnicity-matched controls. Demographic, lifetime occupational history, family history of cancer, lifestyle (e.g., smoking, alcohol, diet, and recreational physical activity) and anthropometric information were collected by personal interviews. Chemical exposure and physical activity were determined using job-exposure matrices for each reported job. RESULTS. Logistic regression models adjusted for relevant covariates were used to evaluate their independent effects. Compared to controls, cases were three times more likely to work in jobs with high agrichemical exposure (OR ¼ 3.44, 95% CI 1.84-6.44), and 54% less likely to work in jobs with moderate/high occupational physical activity (OR ¼ 0.46, 95% CI 0.28-0.77). In analyses stratified by stage, cases with organ-confined PCa were three times more likely to have high agrichemical exposure (OR ¼ 3.39, 9%CI 1.68-6.84), and 56% less likely to have moderate/ high levels of occupational physical activity (OR ¼ 0.44, 95% CI 0.26-0.76). Increased risk of being diagnosed with advanced PCa was associated with obesity at time of diagnosis (OR ¼ 2.50, 95% CI 1.20-5.20) and high levels of agrichemical exposure (OR ¼ 4.65, 95% CI 1.97-10.97), but not with occupational physical activity. CONCLUSIONS. This case-control study, the first conducted in a homogeneous Hispanic population, identified modifiable PCa risk factors, such as physical activity and agrichemical exposure, which may be useful in developing interventions for this understudied population.
The Prostate, 2001
BACKGROUND. Higher prostate cancer mortality rates among US immigrants from countries with lower ... more BACKGROUND. Higher prostate cancer mortality rates among US immigrants from countries with lower rates suggest environmental in¯uences on prostate carcinogenesis (e.g., diet, body composition). METHODS. In a study identifying determinants of clinically relevant prostate cancer, we compared plasma concentrations of leptin, an adiposity-related hormone, in 48 men with tumors 0.5 cc measured after radical prostatectomy and 151 men with tumors b 0.5 cc in volume or with histologic evidence of extraprostatic extension but without metastases (``highvolume disease''), matched by age (AE 5 years) and year at diagnosis (AE 1 year). RESULTS. Men with high-volume disease exhibited higher leptin concentrations overall and after strati®cation by age, testosterone level, height, and body mass index (BMI). Analysis revealed that men with elevated leptin concentrations had an increased risk of diagnosis with high-volume disease (odds ratio (OR) 2.35, 95% con®dence interval (CI) 1.01±5.44), as did men with high leptin and high testosterone (OR 9.73, 95% CI 2.05±46.24) and men ! 5 H 8 HH with high leptin (OR 3.67, 95% CI 1.40±9.63). CONCLUSIONS. Leptin may affect the risk of clinically relevant prostate cancer through testosterone and factors related to stature and obesity.
Nutrition and Cancer, 1999
In the last several years, attention has been focused on comparing the Western diet, which is ric... more In the last several years, attention has been focused on comparing the Western diet, which is rich in fat, protein, and refined carbohydrates, with the Asian diet, which is rich in phytoestrogens, as a possible explanation for the contrasting rates of clinically relevant prostate cancer. Phytoestrogens, plant-derived nutrients, include several isoflavones, flavonoids, lignans, phytosterols, and coumestans, some of which have been postulated as having anticarcinogenic properties. Using a new database, we examined the role of phytoestrogen intake and prostate cancer risk in 83 Caucasian cases and 107 controls. Controls reported consuming higher amounts of foods containing genistein, daidzein, and coumestrol and lower amounts of foods containing campesterol and stigmasterol. Multivariate analysis, after adjustment for age, family history of prostate cancer, alcohol consumption, and total calorie intake, showed an inverse association between coumestrol (p = 0.03) and daidzein (p = 0.07) and prostate cancer risk. Genistein, the most studied phytoestrogen, showed a slight protective effect (p = 0.26). However, a positive association was found between campesterol (p = 0.08) and stigmasterol (p = 0.03) and risk of prostate cancer. These results are suggestive of a possible relationship between phytoestrogen intake and prostate cancer risk. Larger comprehensive studies are needed to further refine the role of phytoestrogen intake in prostate cancer risk.
Nutrition and Cancer, 2005
Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relatio... more Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, b-cryptoxanthin, αand trans-β-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cislycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of α-carotene, trans-β-carotene, β-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-translycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of ≥7, n= 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of β-cryptoxanthin, α-carotene, trans-β-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression.