Estrogen Regulated Genes Compel Apoptosis in Breast Cancer Cells, Whilst Stimulate Antitumor Activity in Peritumoral Immune Cells in a Janus-Faced Manner.

: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women, suggesting that there are serious errors in our preventive and therapeutic measures. Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. 1.

DNA Damage Responses in Tumors Are Not Proliferative Stimuli, but Rather They Are DNA Repair Actions Requiring Supportive Medical Care.

Background: In tumors, somatic mutagenesis presumably drives the DNA damage response (DDR) via altered regulatory pathways, increasing genomic instability and proliferative activity. These considerations led to the standard therapeutic strategy against cancer: the disruption of mutation-activated DNA repair pathways of tumors.

Purpose: Justifying that cancer cells are not enemies to be killed, but rather that they are ill human cells which have the remnants of physiologic regulatory pathways.

Rosetta Stone for Cancer Cure: Comparison of the Anticancer Capacity of Endogenous Estrogens, Synthetic Estrogens and Antiestrogens.

This work presents the history of the recognition of principal regulatory capacities of estrogen hormones having been mistakenly regarded as breast cancer promoting agents for more than 120 years. Comprehensive analysis of the results of clinical, epidemiological, immunological and molecular studies justified that endogenous estrogens are the principal regulators of embryonic development, survival and reproduction orchestrating appropriate expression and even edition of all genes in mammalians. Medical use of chemically modified synthetic estrogens caused toxic complications; thromboembolic events and increased cancer risk in female organs as they proved to be endocrine disruptors deregulating estrogen receptors (ERs) rather than their activators.

Histological Examination of Retrieved ePTFE Membranes Following Regenerative Surgery of Intrabony Defects Treated with Platelet-rich Plasma and Bone Substitutes.

Purpose: Regenerative periodontal therapy using platelet-rich plasma (PRP) and bone substitutes with guided tissue regeneration (GTR) have been proposed as a therapeutic method to enhance the outcome of regenerative surgery. This includes light microscopic evaluation of retrieved ePTFE membranes to assess formation of new connective tissue attachment, and following the regeneration process. The objectives of this study were to evaluate the histological findings of retrieved ePTFE membranes using PRP and bone substitutes, the effect of PRP on graft materials, and the correlation of the findings with the clinical outcomes.

Compensatory Estrogen Signal Is Capable of DNA Repair in Antiestrogen-Responsive Cancer Cells via Activating Mutations.

Cancer cells are embarrassed human cells exhibiting the remnants of same mechanisms for DNA stabilization like patients have in their healthy cells. Antiestrogens target the liganded activation of ERs, which is the principal means of genomic regulation in both patients and their tumors. The artificial blockade of liganded ER activation is an emergency situation promoting strong compensatory actions even in cancer cells.

Prevention and therapy of COVID-19 via exogenous estrogen treatment for both male and female patients.

The presented work summarizes the results of studies underlining the crucial role of estrogen receptor (ER) signaling in both innate and adaptive immune responses as well as in tissue repairing processes during respiratory virus infection. Experimental studies justify that among respiratory virus infected mice, a weaker ER signaling leads to increased morbidity and mortality in both males and females. In animal experiments, estrogen treatment silences the inflammatory reactions and decreases virus titers leading to improved survival rate; it seems to be an ideal prevention and therapy against COVID-19.

Amplified Crosstalk Between Estrogen Binding and GFR Signaling Mediated Pathways of ER Activation Drives Responses in Tumors Treated with Endocrine Disruptors.

Background: The pharmaceutical development of endocrine disruptors could not achieve appropriate advances in the field of anticancer fight.

Objective: Considerations on the principles of currently used endocrine therapies.

Methods: Comparison of the results of genetic studies being performed on breast cancer cells treated with estrogens, synthetic estrogens and antiestrogens.

Activating Mutations of ESR1, BRCA1 and CYP19 Aromatase Genes Confer Tumor Response in Breast Cancers Treated with Antiestrogens.

Background: Four decades of erroneous breast cancer therapy with antiestrogens yielded the chaotic mixture of manifestations of artificial ER-inhibition and compensatory activating ER-mutations together with unreckonable tumor responses.

Objective: Due to the confusions between the anticancer and carcinogenic impacts of antiestrogens and synthetic estrogens, the old principle needs to be revised as concerns ER-signaling induced DNAdamage and breast cancer development.

Method: Results of genetic studies on both estrogen- and antiestrogen-treated tumors were reanalyzed and associations among ER-blockade, compensatory restoration of ER-signaling and clinical behavior of cancers were investigated.

Causal Therapy of Breast Cancer Irrelevant of Age, Tumor Stage and ER-Status: Stimulation of Estrogen Signaling Coupled With Breast Conserving Surgery.

Background: Results of long-term studies justify that the rate of breast cancer recurrence and tumor-related mortality remains quite unpredictable, regardless of the use of any current therapeutic measures.

Objective: Since the application of standard therapies, such as surgery, radiation, chemotherapy and antiestrogen administration does not work as might be expected; our therapeutic practice requires thorough rethinking.

Method: Published long-term therapeutic results on breast cancer cases were analyzed in correlation with stage at diagnosis, ER-status of tumors and patients' age.

[The prognostic role of expression of p16 tumor suppressor gene in Hungarian patients with oral squamous cell carcinoma].

Beside smoking and alcohol consumption, human papillomavirus (HPV) infection is the most common risk factor of squamous cell carcinoma in the head and neck region (HNSCC). The latter group of patients associates with better prognosis. During HPV infection, the level of p16 tumor suppressor elevates, which could give an additional opportunity for diagnosis: instead of molecular diagnostic tools, the application of immunohistochemistry is acceptable.

The pitfall of the transient, inconsistent anticancer capacity of antiestrogens and the mechanism of apparent antiestrogen resistance.

Although antiestrogens have been available for breast cancer therapy since the early 1970s, neither their inconsistent anticancer capacity nor the developing antiestrogen resistance of tumors can be fully understood. Although clinical and experimental investigations revealed many tiny details concerning the link between estrogen signaling and tumor development, they yielded fairly controversial findings. Estrogen receptor (ER) overexpression in tumor cells induced by estrogen treatment was erroneously regarded as a promoter of DNA damage, genomic instability, and tumor growth.

DNA stabilization by the upregulation of estrogen signaling in BRCA gene mutation carriers.

Currently available scientific evidence erroneously suggests that mutagenic weakness or loss of the BRCA1/2 genes may liberate the proliferative effects of estrogen signaling, which provokes DNA damage and genomic instability. Conversely, BRCA mutation seems to be an imbalanced defect, crudely inhibiting the upregulation of estrogen receptor expression and liganded transcriptional activity, whereas estrogen receptor-repressor functions become predominant. In BRCA-proficient cases, estrogen signaling orchestrates the activity of cell proliferation and differentiation with high safety, while upregulating the expression and DNA-stabilizing impact of BRCA genes.

Diverse pathomechanisms leading to the breakdown of cellular estrogen surveillance and breast cancer development: new therapeutic strategies.

Recognition of the two main pathologic mechanisms equally leading to breast cancer development may provide explanations for the apparently controversial results obtained by sexual hormone measurements in breast cancer cases. Either insulin resistance or estrogen receptor (ER) defect is the initiator of pathologic processes and both of them may lead to breast cancer development. Primary insulin resistance induces hyperandrogenism and estrogen deficiency, but during these ongoing pathologic processes, ER defect also develops.

Triple-negative breast cancer risk in women is defined by the defect of estrogen signaling: preventive and therapeutic implications.

Epidemiologic studies strongly support that triple-negative breast cancers (TNBCs) may be distinct entities as compared with estrogen receptor (ER)+ tumors, suggesting that the etiologic factors, clinical characteristics, and therapeutic possibilities may vary by molecular subtypes. Many investigations propose that reproductive factors and exogenous hormone use differently or even quite inversely affect the risk of TNBCs and ER+ cancers. Controversies concerning the exact role of even the same risk factor in TNBC development justify that the biological mechanisms behind the initiation of both TNBCs and non-TNBCs are completely obscure.

Circulatory estrogen level protects against breast cancer in obese women.

Literary data suggest apparently ambiguous interaction between menopausal status and obesity-associated breast cancer risk based on the principle of the carcinogenic capacity of estrogen. Before menopause, breast cancer incidence is relatively low and adiposity is erroneously regarded as a protective factor against this tumor conferred by the obesity associated defective estrogen-synthesis. By contrast, in postmenopausal cases, obesity presents a strong risk factor for breast cancer being mistakenly attributed to the presumed excessive estrogen-production of their adipose-tissue mass.

Light deficiency confers breast cancer risk by endocrine disorders.

North-America and northern European countries exhibit the highest incidence rate of breast cancer, whereas women in southern regions are relatively protected. Immigrants from low cancer incidence regions to high-incidence areas might exhibit similarly higher or excessive cancer risk as compared with the inhabitants of their adoptive country. Additional cancer risk may be conferred by incongruence between their biological characteristics and foreign environment.

[Histological investigations in ambulatory oral surgery practice].

In the practice of oral surgery correspondence with the pathologist is required in order to identify the lesions in question by histologic examination. By current legal regulations the histological evaluation of removed tissues is mandatory. In the presentation the authors process the data obtained in their Department since 2008.

[Interactions of insulin and estrogen in the regulation of cell proliferation and carcinogenesis].

Equilibrium of sexual steroids and metabolic processes has close correlations. Insulin is a potent regulator of human sexual steroid hormone production and modulates their signals at receptor level. Insulin resistance and excessive insulin production provoke hyperandrogenism and estrogen deficiency in women resulting not only in anovulatory dysfunction but also a high risk for cardiovascular diseases and cancer.

Interplay between insulin resistance and estrogen deficiency as co- activators in carcinogenesis.

Both insulin resistance and estrogen deficiency result in complex metabolic disorder based mainly on defective cellular glucose uptake and on an atherogenic serum lipid profile. These alterations may be regarded as high risks for several life-threatening human diseases, such as type-2 diabetes, cardiovascular lesions and malignancies. Insulin resistance and estrogen deficiency are concomitant disorders with mutual interrelationship.

Decreased oral cancer risk by moderate alcohol consumption in non-smoker postmenopausal women.

Objective: Alcohol consumption is a strong risk factor for oral cancer however; an ambiguous biphasic impact of moderate and excessive alcohol intake on the risk of upper aerodigestive tract cancers has also been published. The aim of the present study was to clarify the dose-related risk of alcohol consumption for oral cancer, in male and female cases.

Materials And Methods: Six-hundred and eight non-smoker patients (466 males and 142 females) with squamous cell oral carcinomas (OCs) and 406 non-smoker tumor free controls (264 males and 142 females) were included into the study.

[Surgical-orthodontic treatment of the upper canine retention].

Combined surgical and orthodontic treatment of upper canine retention showed thorough development during the past decade. Depending on the axial position of the unerupted canine there are three methods for their alignment. When the axis of the unerupted canine is near vertical making a mucosal window is enough for deliberation of the crown.

[Etiology and diagnostics of upper canine tooth retention].

Upper canines have significant esthetical and functional roles in the dental arch. Upper canine retention is a frequent anomaly as the germ develops rather far from its final place. Moreover, the neighboring teeth may narrow the place of the canine because of its late eruption.

[Oral cancer: morbus Hungaricus in the 21st century].

Hungary is the leader both in oral cancer morbidity and mortality among the European countries. Oral cancer mortality had increased dramatically in Hungary to near fourfold between 1975 and 2002 both among the male and female populations. The increased oral cancer morbidity among the non-smoker, non-drinker elderly women and young adults, suggest that factors other than tobacco and alcohol consumption may also have important role in the pathogenesis of oral cancer.

[Carcinogenesis theory based on estrogen deficiency].

Earlier, estrogens were considered simply the most important hormones involved in female physiology and reproduction. Nowadays it has become familiar that they have pivotal roles in gene regulation of cell differentiation and proliferation. There are many contradictions concerning the associations of female sexual steroids and cancer.