Treatment Of Mammary Carcinoma Research Articles

Effect of Okra Fruit (Abelmoschus esculentus) Extract on Granzyme Expression and Tumor Mass Diameter of Adenocarcinoma Mammae: An In Vivo Study

Background: Breast cancer is currently one of the most common types of cancer suffered by women, with the highest prevalence in all countries in the world. Herbal plants are thought to increase the immune system against tumors, one of which is okra (Abelmoschus esculentus) has the potential as an anti-tumor and anti-carcinogenic. This study aimed to assess the efficacy of ethanol okra extract on granzyme expression and tumor mass diameter in mammary adenocarcinoma of rats treated with adriamycin-cyclophosphamide chemotherapy.
 Methods: This study is an experimental study using 28 Sprague Dawley Rats. Data analysis was performed with SPSS version 21 to assess differences in granzyme expression and tumor size.
 Results: The combination of chemotherapy and okra fruit extract (P3) showed optimal potential in increasing granzyme expression and reducing mammary tumor size.
 Conclusion: The okra fruit extract has potential in the treatment of mammary carcinoma by increasing the expression of granzymes so as to reduce the size of breast carcinoma tumors in vivo.

Effectiveness of the Nipples-Saving Mastectomy (NSM): Review on the Results, Oncologic Safety and Surgical Complications

Background: The nipples-saving mastectomy (NSM), most recent technique, allows the whole mammary gland removal preserving the nipple-areola compound (NAC), obtaining oncologic safe results. When indicated, NSM is validated by the great aesthetic results obtained. Objectives: The objective of this review is the evaluation of the effectiveness and oncologic safety of the nipple-saving mastectomy, marking the most frequent complications. Moreover, the possibility to use the NSM procedure as prophylactic mastectomy in patients at high risk has been evaluated. Research Methods: A bibliographic research about clinical studies and previous reviews related to nipplessaving mastectomy has been conducted. No limitation about language was performed. Results: The study included 12 articles, for a total of 2859 patients and 3849 NSM. Patients candidate to NSM, either as a prophylactic or curative treatment of mammary carcinoma, must undergo a careful selection screening. Most frequently occurring surgery-related complications were necrosis and infections; though not altering the cosmetic results, that have been positively evaluated in almost all patients. Conclusion: Preservation of the areola-nipple compound seems to be oncologically safe and does not increase local recurrences, compared to the previous techniques. Moreover, it is associated with better aesthetic results and patients’ higher satisfaction.

Protective Effect of Madhuca longifolia Leaves in 7, 12-Dimethylbenz(a)anthracene Induced Mammary Carcinoma in Sprague Dawley Rat model

Objectives: To evaluate the pretreatment with Madhuca longifolia leaves on 7, 12-Dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma in Sprague Dawley rat. Materials and Methods: Thirty female Sprague Dawley rats were divided into five groups, and each group is having six rats. Group I rats received vehicle (1 mL of emulsion of sunflower oil and physiological saline) subcutaneously and 1 mL of 2% dimethyl sulfoxide per orally. Groups II, III, IV, and V were induced mammary carcinogenesis by giving single dose of subcutaneous injection of 25 mg of DMBA. Group III, IV, and V rats were administered with MEML 100, 200 mg/kg and Vincristine 0.5 mg/kg dissolved in 1 ml of 2% dimethylsulfoxide given 1 week before the administration of the carcinogen, respectively, and continued for 16 weeks. At the end of experiment, the animals were sacrificed and biochemical estimations were done in all groups. Mammary tissues in all groups were dissected out and used for histopathological studies. Results: Oral administration of 200 mg/kg of MEML to DMBA-treated rats effectively prevented the tumor incidence, total number of tumors, and tumor volume and brought back the biochemical markers to normal, which was comparable with standard group. In lower dose 100 mg/kg, the effect was very less compared to normal and standard groups. Our data showed that MEML 200 mg/kg significantly restored the breast tissue biochemically and histologically which was comparable with standard. Conclusion: Our results concluded that the leaves of Madhuca longifolia may be used in the treatment of mammary carcinoma.

D-Pinitol a low-molecular cyclitol prevents 7,12-Dimethylbenz [a] anthracene induced experimental breast cancer through regulating anti-apoptotic protein Bcl-2, mitochondrial and carbohydrate key metabolizing enzymes

Compounds of dietary origin have always been considered as a paramount entity due to their popular belief of the absence of adverse side effects and also for their extraordinary efficacy against many diseases among which cancer is most important. The present investigation was aimed to evaluate the modulatory effect of d-Pinitol a compound from dietary origin, on the key mitochondrial tricarboxylic acid cycle, carbohydrate metabolizing enzymes and anti-apoptotic protein Bcl-2 against 7, 12-Dimethylbenz [a] anthracene (DMBA) induced mammary carcinoma in female Sprague Dawley rats. Breast caner was induced by intragastric administration of single dose of 20mg/kg body weight of DMBA. The results revealed that the levels of TCA cycle enzymes and carbohydrate metabolizing enzymes were drastically altered in both breast and liver tissues of cancer-bearing animals when compared to controls. Further, the anti-apoptotic protein Bcl-2 was found to be expressed during breast cancer. Interestingly, the oral administration of d-Pinitol at a dosage of 200mg/kg body weight for 45days to breast cancer-bearing rats were found to be significantly brought back the altered enzymes status to near normal range. This therapeutic activity may be due to the antioxidant property of d-Pinitol, which ultimately results in the mitochondrial compartment. Thus, our results clearly confirmed that d-Pinitol has some key modulatory property in mitochondrial and carbohydrate metabolizing enzymes through its antioxidant nature and also regulatory role in the proteins of anti-apoptotic cascade against the free radicals involved oxidative stress-mediated diseases, and which results in the consideration of the compound as safe and more effective in the treatment of mammary carcinoma in the near future.

Treatment of Mammary Carcinomas in HER-2 Transgenic Mice through Combination of Genetic Vaccine and an Agonist of Toll-Like Receptor 9

Oligodeoxynucleotides containing unmethylated CpG dinucleotides induce innate and adaptive immunity through Toll-like receptor 9 (TLR9). In the present study, we have examined the ability of a novel agonist of TLR9, called immunomodulatory oligonucleotide (IMO), to enhance effects of a HER-2/neu plasmid DNA electroporation/adenovirus (DNA-EP/Ad) vaccine. BALB/NeuT mice were treated with DNA-EP vaccine alone, IMO alone, or the combination of two agents starting at week 13, when all mice showed mammary neoplasia. Tumor growth and survival were documented. Antibody and CD8+ T-cell responses were determined. Peptide microarray analysis of sera was carried out to identify immunoreactive epitopes. Additionally, microCT and microPET imaging was carried out in an advanced-stage tumor model starting treatment at week 17 in BALB/NeuT mice. The combination of DNA-EP and IMO resulted in significant tumor regression or delay to tumor progression. 2-Deoxy-2-[18F]fluoro-D-glucose microPET and microCT imaging of mice showed reduced tumor size in the DNA-EP/IMO combination treatment group. Mice treated with the combination produced greater antibody titers with IgG2a isotype switch and antibody-dependent cellular cytotoxicity activity than did mice treated with DNA-EP vaccine. An immunogenic B-cell linear epitope, r70, within the HER-2 dimerization domain was identified through microarray analysis. Heterologous DNA-EP/Ad vaccination combined with IMO increased mice survival. The combination of HER-2/neu genetic vaccine and novel agonist of TLR9 had potent antitumor activity associated with antibody isotype switch and antibody-dependent cellular cytotoxicity activities. These results support possible clinical trials of the combination of DNA-EP/Ad-based cancer vaccines and IMO.

Changes in protein tyrosine phosphatase type IVA member 1 and zinc finger protein 36 C3H type-like 1 expression demonstrate altered estrogen and progestin effect in medroxyprogesterone acetate-resistant and estrogen-independent breast cancer cell models

Estrogen stimulates proliferation in hormone-responsive breast cancer cells. Progestins inhibit the estrogen-mediated growth in these cells and are used in the treatment of mammary carcinomas. We applied cDNA microarray and real-time RT-PCR methods to reveal 17β-estradiol- and medroxyprogesterone acetate (MPA)-regulated genes in MCF-7 breast cancer cells. We identified six genes, two of which were novel MPA and/or 17β-estradiol-regulated genes: protein tyrosine phosphatase type IVA, member 1 (PTP4A1) and zinc finger protein 36, C3H type-like 1 (ZFP36L1). PTP4A1 expression was upregulated by 17β-estradiol and this was opposed by MPA treatment of the cells. ZFP36L1 proved to be a direct target of MPA. Since MPA has also been shown to bind to glucocorticoid- and androgen receptors, we studied the regulation of the genes with progesterone, synthetic progestin R5020, dexamethasone and dihydrotestosterone. We also assessed the expression and hormonal regulation of PTP4A1 and ZFP36L1 mRNA in MCF-7-derived MPA-resistant and estrogen-independent sublines. The regulation of PTP4A1 expression upon 17β-estradiol and combined 17β-estradiol and MPA treatment was completely reversed in the estrogen-independent and MPA-resistant sublines, respectively. This study suggests an important role for PTP4A1 in cell growth, and shows that MPA may potentiate the effect of 17β-estradiol in the MPA-resistant breast cancer cells.

ErbB2 Transgenic Mice: A Tool for Investigation of the Immune Prevention and Treatment of Mammary Carcinomas

The epidermal growth factor receptor belongs to a superfamily of receptor tyrosine kinases (RTK) that includes ErbB2. ErbB2 is involved in normal physiological processes, such as embryogenesis, cell proliferation, differentiation, adhesion motility, and apoptosis, while its malfunction or overexpression is responsible for development defects, diabetes, and cancer. The human ortholog of ErbB2 is referred as Her-2 (human ErbB2) while the rat ortholog is referred as neu (rat ErbB2). As ErbB2 is directly involved in carcinogenesis, mice transgenic for the rat neu oncogene allow straightforward assessment of the ability of drugs and vaccines to inhibit the progression of neu-driven cancer. Information from this model may provide indications on the efficacy of similar treatments in patients. This commentary provides key information regarding the use of these transgenic mouse models for evaluation of the efficacy of anti-tumor strategies.

3H-Thymidin-Inkorporation unter endokrinem Einfluß und Hormonrezeptorgehalt menschlicher Mammakarzinome

The effect of medroxyprogesterone acetate, oestradiol-17 beta and testolactone on 3H-thymidine incorporation in human mammary carcinoma was studied in vitro. 54% of the tumours reacted to medroxyprogesterone, while testolactone and oestradiol-17 beta changed 3H-thymidine incorporation in 45.1 and 41.3%, respectively. Both inhibition and the in vivo undesirable stimulation of 3H-thymidine incorporation was observed. No relation could be established between oestrogen receptor content and reaction of the mammary carcinoma to oestradiol-17 beta. On the other hand, the gestagen receptor content and the reaction of the mammary carcinoma to medroxyprogesterone acetate correlated significantly (P < 0.001). This underlines the increasing significance of the gestagen receptor in the selective endocrine treatment of mammary carcinoma.

Konservative Primäroperation des Mammakarzinoms: Subkutane Mastektomie, Lymphadenektomie und Bestrahlung

So-called nipple-preserving operations were performed as primary treatment of mammary carcinoma, predominantly in stage T1, in 135 women. The operation consisted of subcutaneous mastectomy, axillary lymphadenectomy, nipple biopsy and X-ray therapy. Most of the patients in whom more than two lymph nodes had carcinomatous changes also received chemotherapy. Survival of more than five years was achieved in 48 patients in stage T1. One woman died of carcinoma; in six there was further growth with metastases. In no case was there further growth in the nipple region. Although the numbers are small one can already state that the results are no worse than after more radical operations.

Role of Neuregulin-1/ErbB Signaling in Cardiovascular Physiology and Disease

Since the discovery that neuregulin-1 (NRG-1)/ErbB signaling is indispensable in cardiac development, evidence has shown that this system also plays a crucial role in the adult heart. In patients, an inhibitory ErbB2 antibody, trastuzumab, used in the treatment of mammary carcinomas, increases the risk for the development of cardiotoxic cardiomyopathy. Postnatal disruption of NRG-1/ErbB signaling by gene targeting in mice leads to dilated cardiomyopathy. Initially, the search for the mechanisms behind these observations focused mainly on the effects of NRG-1 on cardiomyocyte growth and survival and revealed that NRG-1 has Akt-dependent antiapoptotic effects in cultured cardiomyocytes. In vivo studies, however, did not uniformly reinforce a role for apoptosis in the development of cardiomyopathy induced by impaired NRG-1/ErbB signaling. More recent studies have revealed that NRG-1 is involved in the regulation of cardiac sympathovagal balances by counterbalancing adrenergic stimulation of the adult myocardium and through an obligatory interaction with the muscarinic cholinergic system. NRG-1 is synthesized and released by the endocardial and cardiac microvascular endothelium, dynamically controlled by neurohormonal and biomechanical stimuli. The physiology of the cardiac NRG-1/ErbB system has implications for the treatment of both cancer and heart failure. Clinical studies in breast cancer with novel ErbB inhibitors are currently underway. Novel oncological indications for ErbB inhibition are emerging; cardiovascular side effects need to be carefully monitored. On the other hand, pharmacological activation of ErbB signaling is likely an unrecognized and beneficial effect of currently used drugs in heart failure and a promising therapeutic approach to prevent or reverse myocardial dysfunction.

Inhibition by 9α-fluoromedoroxyprogesterone acetate (FMPA) against mammary carcinoma induced by dimethylbenz[ a]anthracene in rats and angiogenesis in the rabbit cornea – comparison with medroxyprogesterone acetate (MPA)

Medroxyprogesterone acetate (MPA) is currently used therapeutically in the treatment of mammary and endometrial carcinomas. In order to develop a more potent and useful drug, we synthesized the novel compound, 9α-fluoromedoroxyprogesterone acetate (FMPA), by fluorinating MPA, and we also previously reported that FMPA displays more potent anti-angiogenic activity in the chorioallantoic membrane assay than MPA. In the present study, we investigated (1) the effects of FMPA on rat mammary carcinomas induced by dimethylbenz[ a]anthracene (DMBA) to determine the anti-tumor activity, (2) the effect on angiogenesis in rabbit corneal assays, and (3) compared these results with those for MPA. FMPA inhibited the growth of mammary carcinomas in a dose-dependent manner (7.5, 30 and 120 mg/kg). Almost complete involution of the carcinomas was observed at doses of 30 and 120 mg/kg. MPA also inhibited the growth of carcinomas at doses of 30 and 120 mg/kg, but no involution of carcinomas was observed even at 120 mg/kg. FMPA significantly and MPA to a lesser degree inhibited carcinogenesis at 120 mg/kg within their treatments. In rabbit corneal assays, FMPA significantly inhibited angiogenesis (IC50 value=0.085 μg/pellet). MPA also significantly inhibited angiogenesis (IC50 value=0.60 μg/pellet). From these results, we conclude that FMPA is potentially more effective in the treatment of mammary carcinomas than MPA.

Progesterone antagonist treatment of mammary-carcinoma after pretreatment with tamoxifen equals the efficacy of progestins: Studies in MXT-, DMBA- and NMU-tumor models

Progesterone antagonist treatment of mammary-carcinoma after pretreatment with tamoxifen equals the efficacy of progestins: Studies in MXT-, DMBA- and NMU-tumor models

Intratumor treatment of C3H mouse mammary carcinoma with 5-fluorouracil adsorbed on activated charcoal particles.

A dosage form comprising 5-fluorouracil (5-FU, 25 mg/ml) adsorbed on a suspension of micronized charcoal (100 mg/ml) 2-5 microns in diameter, adsorbing 5-FU in aqueous solution was studied for intratumor treatment of mammary carcinoma in animal experiments. An in vitro desorption method is described to determine the amount of 5-FU adsorbed on activated charcoal particles which would be released once the drug concentration decreased around the charcoal. In vivo results indicate that an intratumor injection of 5-FU adsorbed on activated charcoal particles is a highly effective method for achieving tumor regression without increasing toxicity.

“Residual” mammary carcinoma following simulated partial mastectomy

Treatment of mammary carcinoma by partial mastectomy rather than by total mastectomy and axillary dissection may diminish the chances of long-term cure by risking incomplete removal of all local carcinoma at the initial operation. This study was undertaken to determine by pathologic examination how often carcinoma might remain in the breast and axilla after partial mastectomy. The operation was simulated in 203 mastectomy specimens after operations for unilateral invasive carcinoma. In so far as could be determined on gross examination, the entire primary lesion was included in the quadrant which was excised in the simulated procedure. Among 100 women with primary lesions less than 2 cm in diameter, 26% had carcinoma in the breast which remained after simulated partial mastectomy. Six percent of them also had axillary node metastases. An additional 30% only had axillary node metastases. When the primary lesion was more than 2 cm in diameter, 38% of patients had carcinoma in the breast after simulated partial mastectomy, of whom 29% also had axillary metastases. After simulated partial mastectomy, carcinoma was found in 80% of breasts from patients with lesions in the subareolar area, in contrast with 25-35% of patients with a primary carcinoma in one of the four quadrants. None of the 9 patients with medullary and colloid carcinomas that measured under 2 cm had axillary metastases or carcinoma in the breast outside of the primary quadrant. The findings suggested that a familial history of breast carcinoma or a large primary lesion may be associated more often with multifocal disease, but factors such as age at diagnosis, axillary status, and the mammogram report did not have significant predictive value for distinguishing between patients who did or did not have carcinoma in breast tissue after the primary had been removed by a simulated partial mastectomy.

Physical Aspects on Dose Planning in Treatment of Mammary Carcinoma

Physical Aspects on Dose Planning in Treatment of Mammary Carcinoma

Physical Aspects on Dose Planning in Treatment of Mammary Carcinoma

Physical Aspects on Dose Planning in Treatment of Mammary Carcinoma

Measurement and treatment of mammary carcinoma in bitches.

Measurement and treatment of mammary carcinoma in bitches.

1 Some Recently Introduced Drugs

This chapter reviews the variety of drugs. The compounds to be studied have been grouped under two main headings: (1) those which are modifications, designed primarily to improve physico-chemical characteristics, of pre-existing drugs; and (2) drugs which are either completely new in structure or activity or are sufficiently different from previously available agents to warrant separate notice. Drostanolone, which is offered as a palliative in the treatment of mammary carcinoma, has stimulated considerable research into anti-oestrogenic mechanisms, while the increasing use of allopurinal (Zyloric) in gout has revealed new aspects of purine metabolism. Cholestyramine is a quaternary ammonium cationic resin used primarily to bind, in the gut, bile salts, which appear to be the main cause of pruritis in obstructive hepatic disease. Angiotensinamide, pentagastrin, tetracosactrin and felypressin are widely used or growing in importance and serve to illustrate how rapidly this branch of medicinal chemistry is expanding. It concludes that antibiotics with antineoplastic activity continue to appear and rubidomycin is currently receiving wide study.

Pregnancy following treatment of mammary carcinoma.

Pregnancy following treatment of mammary carcinoma.

The measurement of oxidation-reduction potentials, pH, and oxygen tension in tumours.

By use of the apparatus and techniques described in the previous paper (Cater, Phillips &amp; Silver 1957 a ) the oxidation-reduction potentials in Walker carcinoma and Jensen rat sarcoma have been investigated, and compared with those of rat muscle, lactating mammary gland, liver, testis and brain. The changes which occur during the treatment of mammary carcinoma in man and the dog are also described. Breathing oxygen caused a rise of oxidation-reduction potential and oxygen tension in all these tissues except Jensen sarcoma. Intravenous injection of 2-methyl-1:4-naphthohydroquinone diphosphate (Synkavit) caused a fall in the oxidation-reduction potentials of all these tissues, as did cysteine, glutathione and cysteinamine, except that cysteine caused a rise and not a fall in grey matter of rat brain. 220 kVp X-rays even in low doses (100 to 200r) caused a potential fall at platinum, palladium or rhodium electrodes. 0·4 MeV γ -rays from 192 Ir were equally effective. No X-ray effect was obtained with a gold electrode, and it is suggested that the fall of potential with platinum, palladium and rhodium electrodes was due to hydrogen generated by the radiation in the tissue fluid. No change in the pH or oxygen tension was observed during irradiation. The experiments indicate the presence in the tissues of some form of ‘redox’ buffering system.