scholarly journals A triple-negative matrix-producing breast carcinoma is arrested by tumor-targeting Salmonella typhimurium A1-R in a PDOX model

2021 ◽  
Author(s):  
Kazuyuki Hamada ◽  
Jun Yamamoto ◽  
Chihiro Hozumi ◽  
Ming Zhao ◽  
Takuya Murata ◽  
...  
Keyword(s):  
Body Weight ◽  
Breast Carcinoma ◽  
Salmonella Typhimurium ◽  
Tumor Targeting ◽  
Tumor Volume ◽  
Triple Negative ◽  
Control Group ◽  
Orthotopic Implantation ◽  
Surgical Orthotopic Implantation ◽  
Clinical Potential

ABSTRACTBackground/AimMatrix-producing breast carcinoma (MPBC), is a rare, recalcitrant and highly aggressive. The present study aimed to determine the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R on a triple-negative MPBC in a patient-derived orthotopic xenograft (PDOX) model.MethodsThe PDOX model was established in the left second mammary gland of a nude mouse by surgical orthotopic implantation (SOI) of the patient triple-negative MPBC PDOX models were randomized into two groups: G1, control group (n=6); G2, tumor-targeting S. typhimurium A1-R group (n=7, intravenous (i.v.) injection via tail vein, weekly, for two weeks). All mice were sacrificed on day 15. Tumor volume and body weight were measured one time per week.ResultsS. typhimurium A1-R arrested tumor growth compared to the control group (P = 0.016).ConclusionThe results of the present study suggest that S. typhimurium A1-R has future clinical potential in triple-negative MPBC patients.

Single-institution experience with neoadjuvant chemotherapy for metaplastic breast cancer (MBC).

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 140-140
Author(s):  
Anna Kaminsky
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Tumor Volume ◽  
Triple Negative ◽  
Volume Reduction ◽  
Tumor Volume Reduction ◽  
Metaplastic Breast Carcinoma

140 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple-negative and neoadjuvant chemotherapy (NAC) is often used in triple-negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive [H score of 10 or less] and HER2 negative or indeterminate [HER2 1+ or 2+ without amplification by FISH]), were identified. Nine of these TNBCs had metaplastic subtype and two groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Average follow-up in MBC group was 43 months and no patients were lost to follow-up. Average tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow-up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%). Follow-up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple-negative paradox is likely not applicable to MBC.

Single institution experience with neoadjuvant chemotherapy for metaplastic breast cancer (MBC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1038-1038 ◽  
Author(s):  
Anna Kaminsky ◽  
Rohit Bhargava ◽  
Kandace P McGuire ◽  
Shannon Puhalla
Keyword(s):  
Breast Cancer ◽  
Breast Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Tumor Volume ◽  
Triple Negative ◽  
Volume Reduction ◽  
Tumor Volume Reduction ◽  
Metaplastic Breast Carcinoma

1038 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for <1% of all breast carcinomas. MBC is frequently triple negative and neoadjuvant chemotherapy (NAC) is often used in triple negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive (H score of 10 or less) and HER2 negative or indeterminate (HER2 1+ or 2+ without amplification by FISH)), were identified. Nine of these TNBCs had metaplastic subtype and 2 groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Mean follow up in MBC group was 43 months and no patients were lost to follow up. Mean tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%).Follow up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple negative paradox is likely not applicable to MBC.

scholarly journals Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 51
Author(s):  
Ellinor I. Peerschke ◽  
Elisa de Stanchina ◽  
Qing Chang ◽  
Katia Manova-Todorova ◽  
Afsar Barlas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Tumor Volume ◽  
Triple Negative ◽  
Antibody Therapy ◽  
Vehicle Group ◽  
Control Group ◽  
Tunel Staining ◽  
Cell Counts

gC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast cancer cells were injected into the mammary fat pad of athymic nu/nu female mice. Mice were segregated into three groups (n = 5, each) and treated with the vehicle (group 1) or gC1qR antibody 60.11 (100 mg/kg) twice weekly, starting at day 3 post-implantation (group 2) or when the tumor volume reached 100 mm3 (group 3). At study termination (d = 35), the average tumor volume in the control group measured 895 ± 143 mm3, compared to 401 ± 48 mm3 and 701 ± 100 mm3 in groups 2 and 3, respectively (p < 0.05). Immunohistochemical staining of excised tumors revealed increased apoptosis (caspase 3 and TUNEL staining) in 60.11-treated mice compared to controls, and decreased angiogenesis (CD31 staining). Slightly decreased white blood cell counts were noted in 60.11-treated mice. Otherwise, no overt toxicities were observed. These data are the first to demonstrate an in vivo anti-tumor effect of 60.11 therapy in a mouse model of triple negative breast cancer.

scholarly journals THE INFLUENCE OF ANEMIA ON PHAGOCYTIC FUNCTIONS AND RESISTANCE TO INFECTION IN MICE

Blood ◽  
1947 ◽  
Vol 2 (Special_Issue_Number_1) ◽  
pp. 117-124 ◽  
Author(s):  
L. JOE BERRY ◽  
EVELYN C. HALLER
Keyword(s):  
Body Weight ◽  
Survival Rate ◽  
Blood Loss ◽  
Salmonella Typhimurium ◽  
Total Body Weight ◽  
Control Group ◽  
Phagocytic Function ◽  
Progressive Development ◽  
Resistance To Infection ◽  
Total Body

Abstract The increase in phagocytic function of neutrophiles of mice was measured during the progressive development of anemia due to blood loss. The animals were bled from the tail, 2 per cent of total body weight being removed twice weekly for nine bleedings. Phagocytosis was 161 per cent of normal at the end of this period, and the erythrocyte totals and hemoglobin values were approximately two thirds of normal. The anemic mice were infected intraperitoneally with a suspension of Salmonella typhimurium and their survival rate was compared with normal mice similarly infected. Twenty-eight of 63 anemic mice survived and 14 of 63 normal mice survived. In a second experiment, mice were subjected to bleeding every third day for nine bleedings, and were then infected along with a control group. One half of the anemic animals were bled for three additional bleedings after the infection. Two of 48 control animals survived, 5 of 47 anemic mice, additionally bled, survived, and 19 of 47 anemic mice, not bled after infection, survived. This suggests that the increase in phagocytosis that accompanies anemia may be, at least in part, responsible for the increased resistance to infection.

scholarly journals TPX2 Derived Vaccine to Inhibit Tumorigenesis and Metastasis in Triple Negative Breast Cancer 

2020 ◽  
Author(s):  
Yueqiang Jiang ◽  
Yan Liu ◽  
Ling Cheng ◽  
Xiaolong Tan ◽  
Jian Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Lung Metastasis ◽  
Triple Negative Breast Cancer ◽  
Tumor Volume ◽  
Triple Negative ◽  
Vaccine Group ◽  
Control Group ◽  
Strong Immune Response ◽  
Ifn Γ

Abstract Background: triple negative breast cancer (TNBC) lacks of treatment approaches rather than other subtypes of breast cancer. However, it characterizes the highest the level of tumor infiltrating lymphocyte (TIL) than other subtypes, indicating the possibility of immunotherapy. Method: female BALB/c background mice are immunized with a TPX2 derived vaccine 4 consecutive times (once a week) from 6 weeks old, and then 4T1 cells are transplanted to the #4 mammary fatpad. Surface tumor volume and No. of lung metastasis were recorded. TIL and splenocyte was collected for T cell subgroup analysis by methods of flow cytometry and IFN-γ ELISPOT. Result: as a result, TPX2 derived vaccine shows moderate effect, shrinking the tumor volume from 804.4 to 504.5 mm3, and decreasing the number of lung metastasis from 16.6 to 6.0 in control group compared to vaccine group. CD8+ T cell ratio are obviously increased in TIL between vaccine group and control group (5.87% vs 3.37%, P=0.0012). And vaccine could induce strong immune response both in tumor site (87.6 vs 7.0, p=0.0004) and system (28.2 vs 3.8, p＜0.0001) through IFN-γ ELISPOT. Conclusion: our result indicated that TPX2 derived vaccine may be an effective approach to inhibit TNBC tumorigenesis and metastasis.

L-Ascorbic Acid Addition to Chitosan Reduces Body Weight in Overweight Women

2014 ◽  
Vol 84 (1-2) ◽  
pp. 5-11 ◽  
Author(s):  
Eun Y. Jung ◽  
Sung C. Jun ◽  
Un J. Chang ◽  
Hyung J. Suh
Keyword(s):  
Ascorbic Acid ◽  
Body Weight ◽  
Fat Body ◽  
Body Weight Gain ◽  
Skinfold Thickness ◽  
The Body ◽  
Control Group ◽  
Percentage Body Fat ◽  
Overweight Women ◽  
Body Weights

Previously, we have found that the addition of L-ascorbic acid to chitosan enhanced the reduction in body weight gain in guinea pigs fed a high-fat diet. We hypothesized that the addition of L-ascorbic acid to chitosan would accelerate the reduction of body weight in humans, similar to the animal model. Overweight subjects administered chitosan with or without L-ascorbic acid for 8 weeks, were assigned to three groups: Control group (N = 26, placebo, vehicle only), Chito group (N = 27, 3 g/day chitosan), and Chito-vita group (N = 27, 3 g/day chitosan plus 2 g/day L-ascorbic acid). The body weights and body mass index (BMI) of the Chito and Chito-vita groups decreased significantly (p < 0.05) compared to the Control group. The BMI of the Chito-vita group decreased significantly compared to the Chito group (Chito: -1.0 kg/m2 vs. Chito-vita: -1.6 kg/m2, p < 0.05). The results showed that the chitosan enhanced reduction of body weight and BMI was accentuated by the addition of L-ascorbic acid. The fat mass, percentage body fat, body circumference, and skinfold thickness in the Chito and Chito-vita groups decreased more than the Control group; however, these parameters were not significantly different between the three groups. Chitosan combined with L-ascorbic acid may be useful for controlling body weight.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Enzyme Activities ◽  
Treated Group ◽  
Control Group ◽  
Puromycin Aminonucleoside ◽  
Low Level ◽  
Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

Systemic Thrombin Generation and Activity Resistant to Low Molecular Weight Heparin Administered Prior to Streptokinase in Patients with Acute Myocardial Infarction

1997 ◽  
Vol 77 (01) ◽  
pp. 057-061 ◽  
Author(s):  
Dennis W T Nilsen ◽  
Lasse Gøransson ◽  
Alf-Inge Larsen ◽  
Øyvind Hetland ◽  
Peter Kierulf
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Molecular Weight ◽  
Body Weight ◽  
Low Molecular Weight Heparin ◽  
Troponin T ◽  
Bleeding Complications ◽  
Control Group ◽  
Low Molecular Weight ◽  
Creatine Kinase Mb

SummaryOne hundred patients were included in a randomized open trial to assess the systemic factor Xa (FXa) and thrombin inhibitory effect as well as the safety profile of low molecular weight heparin (LMWH) given subcutaneously in conjunction with streptokinase (SK) in patients with acute myocardial infarction (MI). The treatment was initiated prior to SK, followed by repeated injections every 12 h for 7 days, using a dose of 150 anti-Xa units per kg body weight. The control group received unfractionated heparin (UFH) 12,500 IU subcutaneously every 12 h for 7 days, initiated 4 h after start of SK infusion. All patients received acetylsalicylic acid (ASA) initiated prior to SK.Serial blood samples were collected prior to and during the first 24 h after initiation of SK infusion for determination of prothrombin fragment 1+2 (Fl+2), thrombin-antithrombin III (TAT) complexes, fibrinopeptide A (FPA) and cardiac enzymes. Bleeding complications and adverse events were carefully accounted for.Infarct characteristics, as judged by creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT), were similar in both groups of patients.A comparable transient increase in Fl+2, TAT and FPA was noted irrespective of heparin regimen. Increased anti-Xa activity in patients given LMWH prior to thrombolytic treatment had no impact on indices of systemic thrombin activation.The incidence of major bleedings was significantly higher in patients receiving LMWH as compared to patients receiving UFH. However, the occurrence of bleedings was modified after reduction of the initial LMWH dose to 100 anti-Xa units per kg body weight.In conclusion, systemic FXa- and thrombin activity following SK-infusion in patients with acute MI was uninfluenced by conjunctive LMWH treatment.

Overtraining of aerobic physical exercise reduce rats (Rattus norvegicus) memory

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Ni Made Ridla Parwata
Keyword(s):  
Body Weight ◽  
Physical Exercise ◽  
Rattus Norvegicus ◽  
Research Method ◽  
Male Rat ◽  
Control Group ◽  
Adult Male Rat ◽  
The Subject ◽  
Heavy Training

Overtraining syndrome is a decrease in physical capacity, emotions and immunity due to training that is too often without adequate periods of rest. Overtraining is often experienced by athletes who daily undergo heavy training with short break periods. This research aims to look at the effect of overtraining aerobic physical exercise on memory in mice. The research method was experimental in vivo with the subject of adult male rat (Rattus Norvegicus) Winstar strain aged 8-10 weeks, body weight 200-250 gr. Divided into three groups, namely the control group, aerobic group and overtraining group. The results of memory tests with water E Maze showed an increase in the duration of travel time and the number of animal errors made by the overtraining group (p = 0.003). This study concludes that overtraining aerobic physical exercise can reduce memory in rat hippocampus.

Liver, Kidney Function Tests and Oxidative Damage During and after Treatment of Salmonella typhimurium Infection in Experimental Local Rabbits

2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Mustafa Salah Hasan ◽  
Ayman Barzan Abdulgafor ◽  
Maher Saber Owain ◽  
Mohammed Ali Hussein ◽  
Qusay Mohammed Aboud ◽  
...  
Keyword(s):  
Single Dose ◽  
Oxidative Damage ◽  
Salmonella Typhimurium ◽  
Infected Group ◽  
Post Treatment ◽  
Kidney Damage ◽  
Control Group ◽  
Post Inoculation ◽  
Group 5 ◽  
Group 2

This study aimed to evaluate the liver, kidney damage caused by S. typhimurium and to estimate the oxidative damage in association with this bacteria. A highly virulent isolates of S. typhimurium were obtained from the department of internal and preventive medicine/ College of Veterinary Medicine/ University of Baghdad. A twenty five local rabbits of both genders with age range (2-4 months) weeks old were used for this study, the rabbits were divided randomly into five groups each group contains 5 rabbits :- group 1: drenched orally with 5 ml of normal saline and consider as control group, group 2: were drenched orally with (5 ml) suspension which contain (5��109 CFU) of Salmonella typhimurium and regarded as infected group, group 3 were drenched orally with (5 ml) suspension which have (5��109 CFU) of Salmonella typhimurium then treated with a single dose of gentamicin alone at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation), group 4 were drenched (5 ml) suspension having (5��109 CFU) of Salmonella typhimurium then treated with a single dose of Ca-EDTA alone at 40mg/kg orally after presence of signs (after 24hrs. post inoculation) and group 5 were drenched (5 ml) suspension that contain (5��109 CFU) of Salmonella typhimurium then treated with a single dose of combined gentamicin at 0.05ml/kg (5mg/ml) orally after presence of signs (after 24hrs. post inoculation) and Ca-EDTA 40mg/kg after presence of signs (after 24hrs. post inoculation).The results of biochemical profile showed a significant increase (p less than 0.05) in ALT, creatinine and urea levels in infected group as compared with control group, while, the treated groups especially group 5 showed a significant improvement in ALT, Urea and creatinine levels which returned to relative normal levels as compared with infected group after 96hrs. post treatment. Also, the results of oxidative stress showed a significant increase in the levels of MDA in G2, G3, G4 and G5 after 48 hrs. post treatment, while the level of GSH showed a significant decrease in the level at 48hrs., both were returned to relative normal levels after 96hrs.post treatment especially in group 5.In conclusion, S. typhimurium can causing liver and kidney damage which is manifested by increase ALT, Urea and Creatinine. Also, MDA and GSH is increased due to salmonellosis.

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