Oviductal Oxygen Homeostasis in Patients with Uterine Myoma: Correlation between Hypoxia and Telocytes.

Oxygen balance is crucial for angiogenesis, immunity, and tissue repair. The human oviduct is essential for reproductive function, and any imbalance in homeostasis leads to fertility disturbances and might be a reason for ectopic pregnancy development. Uterine myoma is a widespread benign tumour, which is often accompanied by infertility. Telocytes have been discussed in the contexts of motility, fibrosis development, and angiogenesis. We observed the oviducts from patients with and without uterine myoma, comparing the expression of HIF-1, HO, VEGF and its receptor, NOS, oestrogen, and progesterone receptors by immunolabeling. The myometrial and oviductal telocytes were also compared in both groups. Biochemical analyses were conducted for FSH, LH, AMH, sFlt, oestrogen, and progesterone in blood samples. Patients with uterine myoma have different expressions of sex steroid receptors and an increased number of telocytes. The decreasing VEFG expression was compensated by the rise in the HIF-1 and NOS expression. Blood biochemical analyses revealed a higher progesterone level and lower AMH in patients with uterine myoma. No differences in sFlt, FSH, and LF were observed. Uterine myoma impacts oviduct oxygen homeostasis and might cause fertility disturbances (uterine and oviductal infertility factors).

The effectiveness of contrast-enhanced spectral mammography and magnetic resonance imaging in dense breasts.

PURPOSE: Breast cancer is the most common cause of death from neoplastic disease in women. Among all breast anatomy types, glandular type is the most problematic concerning evaluation. While digital mammography still remains the basic diagnostic tool, one must be aware of its limitations in dense breasts. Although magnetic resonance imaging (MRI) has greatly improved sensitivity, its specificity is low. Moreover, there are contraindications for MRI for some patients, so a substitute has been searched for. This study was performed to check if contrast-enhanced spectral mammography (CESM) can be a viable option for patients with dense breasts. MATERIAL AND METHODS: The study involved 121 patients with abnormalities detected on base-line diagnostic imaging (ultrasound or mammography). The patients had subsequent examinations, both CESM and MRI performed within a maximum 2-month time interval. The sensitivity and specificity of both methods in the whole group as well as in specific breast structure types were measured and compared. RESULTS: Contrast enhancement was visible in all 121 cases on MRI, while on CESM lack of enhancement was noted in 13 cases. All of those 13 lesions turned out to be benign. There were 40 (33%) benign and 81 (69%) malignant tumours. The analysed group included 53 (44%) glandular type breast patients, 39 (32%) mixed type, and 29 (23%) fatty type. Although MRI proved to be slightly more effective in dense breasts, both methods showed similar results in the whole study group. CONCLUSION: CESM can be used with confidence in patients with glandular breast type when MRI is not available or there are reported contraindications to MRI.

Diagnostic and prognostic relevance of microparticles in peripheral and uterine blood of patients with endometrial cancer.

OBJECTIVES: Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment. MATERIAL AND METHODS: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer. RESULTS: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor. CONCLUSIONS: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.

Telocytes: facts, speculations and myths (Review article).

Telocyte (TC) is an interstitial cell type with a small cellular body and extremely long tentacle-like extensions. TCs were discovered a decade ago and have specifc morphological characteristics, immunohistochemical and secretome profiles, electrophysiological properties, microRNA expression. Moreover, they are different in gene expression from other cells. TCs play an important role in plenty of processes. Apparently, they are involved in homeostasis, remodelling, regeneration, repair, embryogenesis, angiogenesis and even tumorigenesis. "Telocytes need the world", was emphasized by Professor Popescu and it will be actual at any time. This review summarizes particular features of TCs in different organs and systems, emphasizing their involvement in physiological and pathophysiological processes.

Endometrial cancer and hyperplasia rate in women before menopause with abnormal uterine bleeding undergoing endometrial sampling.

Introduction: Abnormal uterine bleeding (AUB) is the most common symptom of endometrial cancer (EC) and endometrial hyperplasia with (AH) or without (EH) atypia. Risk of malignancy and hyperplasia is significantly lower in premenopausal than in postmenopausal women. Only 10% of EC occurs before menopause. Obesity and age are well-recognized risk factors of endometrial cancer. Endometrial sampling is recommended in women at high risk of endometrial malignancy. The primary objective was to determine the incidence of EC, AH and EH in premenopausal women undergoing dilation and curettage (D&C) because of AUB. Additional objective of the study was to estimate the risk of EC and AH in overweight and obese women with two types of AUB: heavy menstrual bleeding (AUB-HMB) and intermenstrual bleeding (AUB-IMB), according to PALM-COEIN classification. Material and Methods: Retrospective study in the population of women undergoing D&C in tertiary hospital because of AUB between Jan-2016 and Dec-2016. The incidence of EC, AH, EH was established. The influence of the variables: age, BMI, AUBHMB/ AUB-IMB on the occurrence of abnormal histology (EC, AH, EH) was evaluated. Finally, the model built by using backward stepwise regression and mechanism of v-fold cross-validation, showed no statistically significant relationship. Results: EC was detected in 2/213 cases (0.9%; 95% CI 0.0003 to 0.036), AH in 3/213 cases (1.4%), giving a total of 5/213 (2.3%) women with AH or EC. EH was detected in 16/213 (7.5%) women. High BMI raises the chance of AH diagnosis: OR 1.16 (95% CI 1.05- 1.28). The presence of HMB compared to IMB reduces the chance of EH: OR 0.24 (95% CI 0.07-0.9). IMB increases the chance for the diagnosis of EH 4.11 times compared to HMB (OR 4.1, 95% CI 1.1-14.9; p = 0.016). Conclusions: EC in premenopausal women with AUB undergoing D&C is rare. There is a need to search for more effective methods of selection of patients than commonly used. Age and BMI do not seem to be factors that should be used to select patients.

Fertility-sparing treatment in female genital cancer and breast cancer.

Postponed motherhood is the reason why many women are diagnosed with cancer before they make the decision to conceive a child, but only a small number of the affected patients will receive any information about treatment-related infertility As far as female genital cancer is concerned, cervical cancer continues to be the most frequently diagnosed malignancy in women of childbearing age. In its early stages, it can be treated with surgical procedures which spare the genitals, i.e. surgical conization and vaginal radical trachelectomy with laparoscopic lymphadenectomy The advantages of these procedures have been observed in our experience. Also, a successful conservative 6-month treatment of endometrial cancer limited to the mucous membrane with progestagens following curettage of the uterine cavity has been reported in the literature. This paper also presents our own experience with fertility-sparing surgical treatment of ovarian cancer with borderline malignancy and invasive IA stage. Breast cancer affects over 7% of all cancer patients under the age of 40. Pregnancy after breast cancer treatment has been shown to develop properly and both, pregnancy and breastfeeding have no influence on cancer relapse. Protective shields for the adnexa or relocation of the ovaries should be used during radiotherapy in patients who wish to preserve their fertility In case of chemotherapy application of GnRH analogs has shown promising results in preservation of the ovarian function. Also, the development of new assisted reproductive technology has offered an increasing number of alternatives for young cancer patients who wish to preserve their fertility

[Conization and radical vaginal trachelectomy with laparoscopic lymphadenectomy in fertility-sparing surgical treatment of cervical cancer]. / Konizacja i radykalna pochwowa trachelektomia z laparoskopowa limfadenektomia w leczeniu chirurgicznym kobiet z rakiem szyjki macicy pozwalajacym na zachowanie plodnosci.

INTRODUCTION: In the mid-80's and 90's of the last century uterine-sparing surgical treatment methods were proposed to women wishing to preserve their fertility. OBJECTIVES: The aim of the study was to assess practical application of conization or radical vaginal trachelectomy with laparoscopic lymphadenectomy in women with squamous cell cervical cancer (FIGO stages IA and IB1) who want to retain their ability to procreate. Material and methods: A total of 119 women (aged 25-43 years) were included in the study Ninety-six women (60 - IA1 and 36 - IA2) were deemed eligible for conization and 23 women with stages IA2 and IB1 with neoplastic changes of <2cm in diameter were qualified for radical vaginal trachelectomy with laparoscopic lymphadenectomy RESULTS: Conization was not radical in 9 cases and these women were reoperated. A 5-year follow-up in patients after conization revealed disease recurrence (CIN) in 3 IA1 cases (6.5%), and 2 IA2 cases (9.1%). In patients with follow-up of <5 years, no recurrence was observed in 9 out of 10 A1 cases. Similarly there was no recurrence in 7 out of 9 lA2 cases. A 5-year follow-up in patients after trachelectomy confirmed disease recurrence (CIN) in 1 IA2 case (6.25%). There was no disease recurrence in 2 IA1 cases and 4 IB1 cases. Out of 8 subjects staged 1A2 with a follow-up of <5 years, no disease recurrence was observed in 7 (87.5%) patients. During the same follow-up time, no disease recurrence was detected in 3 patients staged IB1. CONCLUSIONS: Proper uterine-sparing treatment with appropriate qualification guarantees adequate control of the treatment process in women with cervical cancer stages IA and IB1 (<2 cm in diameter) according to FIGO.

[Fertility-sparing surgical management of ovarian cancer]. / Leczenie chirurgiczne raka jajnika z zachowaniem plodnosci.

INTRODUCTION: Ovarian cancer (OC) continues to be one of the greatest challenges of modern oncology gynecology Most patients are diagnosed in the advanced stage of the disease, which requires aggressive and extensive surgical intervention. In approximately 8% of the cases, OC affects women <40 years of age. Among them, early-stage OC FIGO IA accounts for 40% of the affected individuals, which allows for fertility-sparing surgical management. OBJECTIVES: The aim of the study was to evaluate the efficacy of fertility-sparing management in OC women, with tumor limited to one ovary who wish to preserve their fertility MATERIAL AND METHODS: A total of 43 women with OC limited to one ovary (26 with borderline malignant tumors and 17 with invasive tumor FIGO IA) underwent surgical sparing therapy Disease recurrence rate as the measure of the quality of treatment and the number of pregnancies, together with their course, as the measure of the effectiveness of the fertility-sparing therapy were evaluated. RESULTS: The observation period, from 4-10 years for borderline malignancy and 3-8 years for invasive FIGO IA tumor revealed no cases of disease recurrence. In the former group, 14 (73 %) women conceived, out of whom 2 miscarried before 22 weeks of gestation, 1 give birth pre-term, i.e. at 34 weeks of gestation, 10 (71.5%) gave birth at term, and 1 is pregnant (6 months) at the time of the publication of the study In the later group, 9 (81.8%) women conceived, out of whom 1 miscarried at 10 weeks of gestation, 1 had a case of intrauterine fetal demise at 27 weeks of gestation, 6 gave birth at term, and 1 is pregnant (3 months) at the time of the publication of the study CONCLUSIONS: Proper patients selection for fertility-sparing management, as well as the way of performing the surgery allow for adequate control of the malignant process in patients with tumor limited to one ovary and preservation of fertility

[Pregnancy and labor after fertility-sparing surgical management of cervical cancer]. / Ciqza i poród u kobiet po oszczedzajacym chirurgicznym leczeniu raka szyjki macicy.

OBJECTIVE: The aim of the study was to evaluate the possibility of conception and the course of pregnancy in women with cervical cancer (FIGO IA and IB1), who underwent fertility-sparing surgical management, i.e. surgical conization or radical vaginal trachelectomy with laparoscopic lymphadenectomy. MATERIAL AND METHODS: A total of 80 patients treated surgically due to cervical cancer constituted the study group. Out of them, 65 (85%) women underwent surgical conization (43--FIGO IA1 and 25--FIGO IA2), and 12 (15%) women underwent radical vaginal trachelectomy with laparoscopic lymphadenectomy (9--FIGO IA2 and 3--FIGO lB1). Cervical cerciage was performed in all patients after trachelectomy. RESULTS: A total of 52 (76.5%) women after surgical conization successfully conceived. Out of them, 3 (5.8)% women miscarried (1 before 12 and 2 between 12-22 weeks of gestation), 2 (3.8%) delivered pre-term (at 26 and 34 weeks of gestation), and 47 (90.4%) delivered at term, including 5 (10.2%) cesarean deliveries, 1 (2.0%) vaginal delivery with the use of the Bracht Manoeuve; and 43 (87.8%) normal vaginal deliveries. Six (50.0%) women after radical vaginal trachelectomy successfully conceived. Out of them, 1 (16.7%) woman miscarried (at 19 weeks of gestation), 2 (33.3%) delivered pre-term (between 22-32 weeks of gestation), and 3 (50%) delivered at term, including 1 (20%) vaginal delivery at 25 weeks of gestation and 4 (80%) cesarean deliveries (1 at 29 weeks of gestation and 3 at term). CONCLUSIONS: Fertility-sparing surgical management in subjects with early-stage cervical carcinoma, provided the patients have been properly qualified for the procedure, allows a significant number of the affected women to conceive, have a normal pregnancy and delivery

[Colposcopic-histologic eligibility criteria for fertility-sparing surgical management in early-stage cervical cancer]. / Kwalifikacja kolposkopowo-histologiczna wczesnych postaci raka szyjki macicy do oszczedzajacego narzad rodny leczenia chirurgicznego.

BACKGROUND: The decision whether fertility-sparing surgical management may be successfully applied in women with cervical cancer who wish to preserve their fertility remains a great therapeutic challenge. Such management is possible if no node metastases are expected and the risk of cancer spread beyond the cervix is limited. Thus, precise evaluation of tumor size is necessary. OBJECTIVES: The aim of the study was to establish cytologic, colposcopic and histologic eligibility criteria for fertility-sparing treatment in women with early-stage cervical cancer. MATERIAL AND METHODS: The study included 119 women (aged 25-43 years) diagnosed and operated on due to malignant changes within the cervix. Each subject underwent cytologic and colposcopic examination, followed by histologic evaluation of a large, target section from the most suspicious area of the lesion. RESULTS: Histologic evaluation revealed stage IA1 in 60 (50.4%), IA2 in 53 (44.5%), and IB1 in 6 (5.1%) patients. Histologic compatibility between target sections and evaluation of the surgical material was 59 (98.4%), 51 (96.2%), and (100%) for stages IA1, IA2, and IB1, respectively CONCLUSIONS: Proper colposcopic assessment of early-stage invasive cervical cancer (IA) allows to identify the most adequate area for large wedge biopsy That in turn makes it possible to establish proper histologic pre-treatment diagnosis, with an over 95% compatibility with the final histologic evaluation, what conditions fertility-sparing surgical treatment.

[Cesarean scar pregnancy]. / Ciaza w bliznie po cieciu cesarskim.

Pregnancy in the uterine scare after previous caesarean section is the rarest type of ectopic pregnancy Due to the possibility of life-threatening complications, cesarean scar pregnancy (CSP) needs rapid and proper diagnosis and management. Hereby we present 3 cases of women with CSP, diagnosed and treated at the Department of Gynecology and Obstetrics of Jagiellonian University Medical College, in Krakow, in 2013, as well as literature review.

Cancer treatment in pregnant women.

In general, strategies for the treatment of cancer in pregnancy should not differ significantly from the treatment regimens in non-pregnant women. However, this is difficult due to either the effects of anticancer drugs on the developing foetus or the possibility of long-term complications after the exposure to drugs and radiation. The decision about the introduction and continuation of treatment in the event of pregnancy should be preceded by a detailed analysis of the potential benefits and risks. There are no data to suggest that pregnancy termination alters the biological behaviour of the tumour or patient prognosis in the presence of appropriate antineoplastic therapy. All patients should be given appropriate advice and informed that there are insufficient scientific data to determine any generally accepted consensus. It is very important to always respect the will of the patient, and the moral judgment of the physician should have no impact on the decisions taken by the woman. If the woman decides to undergo active treatment and maintain her pregnancy, it is necessary to carry out consultations with experts in the field appropriate to the type of cancer. This paper presents a basic review of the literature on the targeted therapies currently used in selected cancers diagnosed during pregnancy: breast cancer, cervical cancer, Hodgkin's disease, melanoma, thyroid cancer, ovarian cancer, and colorectal cancer.

Transrectal ultrasound-guided hysteroscopic myomectomy of submucosal myomas with a varying degree of myometrial penetration.

STUDY OBJECTIVE: To predict the 1-step complete resection rate after transrectal ultrasound-guided hysteroscopic myomectomy and to determine the usefulness of intraoperative transrectal ultrasonography (TRUS) in monitoring hysteroscopic electroresection of submucosal myomas. DESIGN: Prospective cohort study (Canadian Task Force classification II-1). SETTING: University hospital. PATIENTS: One hundred twenty women with symptomatic (abnormal uterine bleeding or reproductive disorder), single, submucosal myomas underwent hysteroscopic electroresection. Groups 1 and 2 were monitored, respectively, with or without TRUS. Anatomical inclusion criteria were myoma ≤5 cm and myometrial free margin ≥3 mm above the myoma. INTERVENTIONS: Myomas were evaluated preoperatively via sonohysterograpy and were graded according to the guidelines outlined by the European Society of Hysteroscopy (ESH), including size and myometrial free margin, and according to the STEPW (size, topography, extension, penetration, and lateral wall) classification. On the basis of sonographic findings, patients with myomas >3 cm received gonadotropin-releasing hormone therapy for 1 to 3 months. Hysteroscopic myomectomy was performed with or without TRUS guidance. At 4 to 8 weeks after the initial procedure, postoperative transvaginal ultrasonography, sonohysterography, or second-look hysteroscopy was performed. MEASUREMENTS AND MAIN RESULTS: In the TRUS group, a significantly higher percentage of 1-step complete resections was observed than in the group without TRUS (91% vs 73%) (p = .02). This was associated with a statistically significant difference in the subgroups of myomas that were deeply penetrating into the myometrium (89% vs 55%) (p < .01). One-way logistic analysis of data for all treated patients indicated the use of TRUS, as well as the ESH and STEPW classifications, as significant factors influencing the 1-step complete resection. At multivariable logistic regression analysis, use of TRUS (odds ratio [OR], 2.74; p < .001), myomas graded 0 or 1 according to ESH (OR, 3.55; p < .001), and size <3 cm (OR, 2.35; p < .05) were significantly associated with 1-step complete resection (area under the curve, 0.80; p < .001). In the TRUS group there were two significant predictors: size <3 cm (OR = 5.21; p < .05) and myometrial free margin <5 mm (OR, 0.18; p < .05). CONCLUSION: Intraoperative use of TRUS during hysteroscopic myomectomy increases the chance of complete 1-step removal of submucosal myomas that deeply penetrate the myometrium.

Relationship between the gut microbiome and endometriosis and its role in pathogenesis, diagnosis, and treatment: a systematic review.

Endometriosis is a chronic inflammatory disease affecting approximately 10% of women. It is defined as endometrial tissue outside of the uterus and produces a variety of symptoms including pelvic pain, dysmenorrhea, dyspareunia, and intermenstrual bleeding. Although several theories have been postulated regarding the pathogenesis of endometriosis, no theory has provided a complete explanation, therefore limiting our progress in diagnostic tools and management of endometriosis. Recently, much attention has been paid to the importance and role of the gut microbiome in endometriosis. As defined by Joshua Lederberg - microbiome is a set of the genome of microorganisms inhabiting a human body, including commensal, symbiotic and pathogenic microorganisms. The aim of this systematic review was to conduct a search in the Embase, Medline, and PubMed databases for literature from July 2013 to July 2023 regarding the relationship between the gut microbiome and endometriosis. 147 records were screened, of which 26 met the eligibility criteria, and 16 were included in this review. Our review concludes that patients with endometriosis show an altered gut microbiome, and that this has the potential to provide insight for pathogenesis, markers for diagnosis, as well as therapeutic options for treatment of endometriosis. Future research is necessary to confirm this and further investigate the relationship between the gut microbiome and endometriosis.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in Poland: analysis of patient series and practical guidelines for breast surgeons.

Introduction: Although breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is infrequent, with less than 1000 noted cases worldwide, patients consenting for breast implant surgery should be aware of its risk. We describe the first Polish multicenter case-series data on BIA-ALCL patients and present diagnostic and treatment recommendation for breast surgeons. Material and methods: In cooperation with the Polish Society of Surgical Oncology and Polish Lymphoma Research Group, we collected BIA-ALCL cases in Poland. Results: We retrospectively reviewed clinical data of seven BIA-ALCL patients, diagnosed between July 2013 and November 2019. The median time from implant placement to the first BIA-ALCL symptoms was 65 months (range: 33-96 months). All the patients were exposed to textured implants at presentation. Capsulectomy with implant removal was performed in all the patients with immediate reimplantation in 2 cases. In a median follow-up of 19 months (range 5-81 months), there was no recurrence and all the patients stayed alive. Between 2013 and 2019, the incidence of BIA-ALCL in Polish female population age 30 and above ranged from 0 to 0.021/100 000/year. Conclusions: BIA-ALCL is scarce in the Polish population. In a short-term follow-up, patients' prognosis remains excellent. Due to the withdrawal of roughly textured implants from the market and the exclusion of likely the most potent etiologic factor, it might be expected that the incidence of BIA-ALCL will become even rarer.

Analysis of RCAS1 immunoreactivity within hydatidiform mole cells and decidual cells according to the applied therapeutic strategy: surgery or surgery followed by chemotherapy.

INTRODUCTION: Trophoblast cells cooperate with both maternal immune cells and decidual cells to help develop the suppressive microenvironment of the endometrium. The maternal immune response against hydatidiform mole depends on this suppressive endometrial profile. Since RCAS1 is one of the molecular factors participating in the development of the suppressive profile of the endometrium we decided to examine the immunoreactivity of the RCAS1 within both the trophoblast and decidual cells during the development of hydatidiform mole. METHODS: We analyzed the immunoreactivity of RCAS1 on both trophoblast and decidual cells derived from patients who underwent curettage because of hydatidiform mole. These patients were then divided into two subgroups according to whether or not they required chemotherapy after the surgical procedure. RESULT: We observed significantly lower immunoreactivity levels of both RCAS1 within the complete molar lesions of the patients on whom surgery alone was performed when compared to the levels found in those for whom surgery was followed by chemotherapy. CONCLUSION: RCAS1 staining may provide information regarding the intensity of the immunosuppressive microenvironment of both the molar lesion and the endometrium. This information can prove significant in determining the clinical course of hydatidiform mole.

DFF45 expression in human endometrium is associated with menstrual cycle phases and decreases after menopause.

BACKGROUND: Human endometrium undergoes cyclic structural and functional modifications, and if no conception occurs menstruation is observed as the result of endometrial cell apoptosis via DFF40/DFF45 complex activation. In postmenopausal endometrium, the proliferative potential of endometrial cells is decreased, while their susceptibility to apoptosis increases. METHODS: The study group comprised 104 nonpregnant adult women (78 of reproductive age and 36 after menopause) with no neoplasm or hormonal treatment during the past 6 months. Immunohistochemistry and Western blot methods were used for DFF45 identification and semiquantitative assessment of its amount. RESULTS: Significantly more DFF45-positive cells were detected in the endometrial glands compared to stroma, and this pattern was constant throughout the whole menstrual cycle and also present in postmenopausal endometrial species. The lowest mean relative amount of DFF45 was detected in postmenopausal endometrial samples. In women of reproductive age, the highest mean relative amount of DFF45 was identified in an early secretory phase of the menstrual cycle, the lowest median value of the relative amount of DFF45 was observed in the late proliferative phase, and the difference was significant. CONCLUSION: The DFF45 level in human endometrium corresponds to the respective phase of the menstrual cycle and decreases significantly after menopause.

Breast cancer chemotherapy induces vascular dysfunction and hypertension through a NOX4-dependent mechanism.

Cardiovascular disease is the major cause of morbidity and mortality in breast cancer survivors. Chemotherapy contributes to this risk. We aimed to define the mechanisms of long-term vascular dysfunction caused by neoadjuvant chemotherapy (NACT) and identify novel therapeutic targets. We studied arteries from postmenopausal women who had undergone breast cancer treatment using docetaxel, doxorubicin, and cyclophosphamide (NACT) and from women with no history of such treatment matched for key clinical parameters. We explored mechanisms in WT and Nox4-/- mice and in human microvascular endothelial cells. Endothelium-dependent, NO-mediated vasodilatation was severely impaired in patients after NACT, while endothelium-independent responses remained normal. This was mimicked by a 24-hour exposure of arteries to NACT agents ex vivo. When applied individually, only docetaxel impaired endothelial function in human vessels. Mechanistic studies showed that NACT increased inhibitory eNOS phosphorylation of threonine 495 in a Rho-associated protein kinase-dependent (ROCK-dependent) manner and augmented vascular superoxide and hydrogen peroxide production and NADPH oxidase activity. Docetaxel increased expression of the NADPH oxidase NOX4 in endothelial and smooth muscle cells and NOX2 in the endothelium. A NOX4 increase in human arteries may be mediated epigenetically by diminished DNA methylation of the NOX4 promoter. Docetaxel induced endothelial dysfunction and hypertension in mice, and these were prevented in Nox4-/- mice and by pharmacological inhibition of Nox4 or Rock. Commonly used chemotherapeutic agents and, in particular, docetaxel alter vascular function by promoting the inhibitory phosphorylation of eNOS and enhancing ROS production by NADPH oxidases.

The analysis of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) immunoreactivity within the microenvironment of the ovarian cancer lesion relative to the applied therapeutic strategy.

RCAS1 is involved in generating the suppressive profile of the tumor microenvironment that helps cancer cells evade immune surveillance. The status of the cells surrounding the cancer nest may affect both the progression of the cancer and the development of metastases. In cases of ovarian cancer, a large number of patients do not respond to the applied therapy. The patient's response to the applied therapy is directly linked to the status of the tumor microenvironment and the intensity of its suppressive profile. We analyzed the immunoreactivity of RCAS1 on the cells present in the ovarian cancer microenvironment in patients with the disease; these cells included macrophages and carcinoma-associated fibroblasts. Later we analyzed the immunoreactivity levels within these cells, taking into consideration the clinical stage of the cancer and the therapeutic strategy applied, such as the number of chemotherapy regiments, primary cytoreductive surgery, or the presence of advanced ascites. In the patients who did not respond to the therapy we observed significantly higher immunoreactivity levels of RCAS1 within the cancer nest than in those patients who did respond; moreover, in the non-responsive patients we found RCAS1 within both macrophages and carcinoma-associated fibroblasts. RCAS1 staining may provide information about the intensity of the immuno-suppressive microenvironment profile found in cases of ovarian cancer and its intensity may directly relate to the clinical outcome of the disease.

[Assessement of the usefulness of whole body scintigraphy after administration of 6 MBq of 131I in the diagnostic of breast cancer]. / Ocena mozliwosci zastosowania scyntygrafii calego ciala po podaniu 6 MBq 131I w diagnostyce raka sutka.

INTRODUCTION: Sodium-iodine symporter (NIS) belongs to a large family of natrium dependent ion transporters found in normal thyroid cells located on the basilar membrane of tyreocytes. Under physiologic conditions, the NIS is also present in other tissues: salivary glands, gastric mucosa, mammary glands during lactation, and vascular plexus of the fourth ventricle. NIS expression has also been found in many tumors, including breast cancer. AIM: The aim of this study was to evaluate the usefulness of whole body scintigraphy after administration of relatively low activity of 131I (6 MBq)in the diagnostics of breast cancer. MATERIAL AND METHODS: The study included nine women with breast cancer, aged 38-73 years (mean 55.6 +/- 11.7 years) and a control group of 14 women aged 29-84 years (mean 48.8 +/- 16.7 years). The uptake of radioiodine in whole body scintigraphy 24 hours after administration of 131I radioiodine (6 MBq) was compared between the control group and breast cancer patients. No pharmaceuticals reducing thyroid iodine uptake or increasing NIS expression were used. RESULTS: Whole body scans using 6 MBq 131I activity revealed no focal radioiodine uptake outside the thyroid tissue in patients with breast cancer as well as volunteers from the control group. CONCLUSIONS: Whole body scintigraphy using 131I, dosed at 6 MBq, with no additional treatment increasing extrathyroidal uptake of radioiodine, appears to be ineffective in the imaging of breast cancer.