Cancer Stem Cell Markers-Clinical Relevance and Prognostic Value in High-Grade Serous Ovarian Cancer (HGSOC) Based on The Cancer Genome Atlas Analysis.

Cancer stem cells (CSCs) may contribute to an increased risk of recurrence in ovarian cancer (OC). Further research is needed to identify associations between CSC markers and OC patients' clinical outcomes with greater certainty. If they prove to be correct, in the future, the CSC markers can be used to help predict survival and indicate new therapeutic targets. This study aimed to determine the CSC markers at mRNA and protein levels and their association with clinical presentation, outcome, and risk of recurrence in HGSOC (High-Grade Serous Ovarian Cancer). TCGA (The Cancer Genome Atlas) database with 558 ovarian cancer tumor samples was used for the evaluation of 13 CSC markers (ALDH1A1, CD44, EPCAM, KIT, LGR5, NES, NOTCH3, POU5F1, PROM1, PTTG1, ROR1, SOX9, and THY1). Data on mRNA and protein levels assessed by microarray and mass spectrometry were retrieved from TCGA. Models to predict chemotherapy response and survival were built using multiple variables, including epidemiological data, expression levels, and machine learning methodology. ALDH1A1 and LGR5 mRNA expressions indicated a higher platinum sensitivity (p = 3.50 × 10-3; p = 0.01, respectively). POU5F1 mRNA expression marked platinum-resistant tumors (p = 9.43 × 10-3). CD44 and EPCAM mRNA expression correlated with longer overall survival (OS) (p = 0.043; p = 0.039, respectively). THY1 mRNA and protein levels were associated with worse OS (p = 0.019; p = 0.015, respectively). Disease-free survival (DFS) was positively affected by EPCAM (p = 0.004), LGR5 (p = 0.018), and CD44 (p = 0.012). In the multivariate model based on CSC marker expression, the high-risk group had 9.1 months longer median overall survival than the low-risk group (p < 0.001). ALDH1A1, CD44, EPCAM, LGR5, POU5F1, and THY1 levels in OC may be used as prognostic factors for the primary outcome and help predict the treatment response.

The Prognostic Value of Cancer Stem Cell Markers (CSCs) Expression-ALDH1A1, CD133, CD44-For Survival and Long-Term Follow-Up of Ovarian Cancer Patients.

Recurrent disease and treatment-associated chemoresistance are the two main factors accounting for poor clinical outcomes of ovarian cancer (OC) patients. Both can be associated with cancer stem cells (CSCs), which contribute to cancer formation, progression, chemoresistance, and recurrence. Hence, this study investigated whether the expression of known CSC-associated markers ALDH1A, CD44, and CD133 may predict OC patient prognosis. We analyzed their expression in primary epithelial ovarian cancer (EOC) patients using immunohistochemistry and related them to clinicopathological data, including overall survival (OS) and progression-free survival (PFS). Expression of ALDH1A1 was detected in 32%, CD133 in 28%, and CD44 in 33% of cases. While Kaplan-Meier analysis revealed no association of the expression of CD133 and CD44 with PFS and OS, ALDH1A1-positive patients were characterized with both significantly shorter OS (p = 0.00022) and PFS (p = 0.027). Multivariate analysis demonstrated that the expression of ALDH1A1, FIGO stage III-IV, and residual disease after suboptimal debulking or neoadjuvant chemotherapy correlated with shorter OS. The results of this study identify ALDH1A1 as a potential independent prognostic factor of shorter OS and PFS in EOC patients. Therefore, targeting ALDH1A1-positive cancer cells may be a promising therapeutic strategy to influence the disease course and treatment response.

Semaphorin 3A (SEMA3A), protocadherin 9 (PCdh9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of different neoplasms, including ovarian cancer - review of literature.

Ovarian cancer is the fifth leading cause of cancer-related deaths in women. Its high mortality rate results from lack of adequate and sensitive methods allowing for the detection of the early stages of the disease, as well as low efficiency of the treatment, caused by the cytotoxic drug resistance of cancer cells. Unfortunately, tumours are able to develop new pathways and protective mechanisms that allow them to survive toxic conditions of chemotherapy. Therefore, intensive search for new genes and proteins involved in resistance to cytotoxic drugs is still needed, especially from a clinical point of view. The article presents an overview of the available literature on the role of semaphorin 3A (SEMA3A), protocadherin 9 (PCDH9), and S100 calcium binding protein A3 (S100A3) in carcinogenesis and chemoresistance of various tumors including ovarian cancer. As it turns out, the role of described genes/proteins is not limited only to their native biological activity but they function also as an oncogenic or suppressor factors in the tumor development. Moreover, they can also play an important role in development of drug resistance, as it was shown in ovarian cancer cell lines.

The value of an initial drop in human Chorionic gonadotropin levels in predicting a response to methotrexate in women with low-risk gestational trophoblastic neoplasia.

OBJECTIVES: The early identification of patients who are being treated for low-risk gestational trophoblastic neoplasia (LRGTN) with single-agent chemotherapy, who are at high risk of developing chemoresistance, is of crucial importance. The aim of our research was to evaluate the pretreatment beta subunit of human chorionic gonadotropin (ßhCG) concentration and its decrease after the administration of the first course of methotrexate (MTX) in predicting later chemo-resistance to single-agent chemotherapy. MATERIAL AND METHODS: A total of 46 patients diagnosed with LRGTN treated with a 5-day methotrexate (MTX) regimen were retrospectively studied. 24 of the patients were successfully cured with only MTX therapy (MTX group). The disease was considered resistant in the remaining 22 patients who, after MTX therapy, required further chemotherapy with an EMA/CO regimen (EMA/CO group). To compare changes in the ßhCG concentrations between the two courses of treatment (and the two groups), we calculated the percentage of decline. We determined the specificity and sensitivity of the initial ßhCG level and its percentage decline, as a potential predictor of the need for a future EMA/CO regimen. For diagnostic purposes, ßhCG levels were measured before the first and second administrations of MTX with a commercial ELISA kit. RESULTS: In the EMA/CO group, we found the initial ßhCG level before the first MTX dose was higher (median = 6275 mIU/mL, range: 21.53-192.610.0 mIU/mL) than in the MTX group (median = 532 mIU/mL, range: 56.5 mIU/mL-360.397.0 mIU/mL) (p = 0.034, Mann-Whitney test). The percentage decreases in the ßhCG values relative to the initial concentrations were higher in the MTX group (median decrease = 82.7%, range: from 13.3% to 99.9%) than in the EMA/CO group (median de- crease = 71.1%, range: from an increase of 56.1% to a decrease of 97.1%) (p = 0.0079, Mann-Whitney test). An analysis of the ROC curves implied optimal cutoff values for the initial ßHCG (6054 IU, sensitivity = 55%, specificity = 86%) and the percentage change in ßhCG levels (decrease by 76.5%, sensitivity = 72%, specificity = 71%). CONCLUSIONS: Women with initially higher ßhCG levels have a greater risk of developing MTX chemo resistance. It would be advantageous to consider administering an EMA/CO regimen in women with LRGTN when their initial ßhCG levels are greater than 6000.

Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy.

OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. MATERIAL AND METHODS: 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill's scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. RESULTS: 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p < 0.0001), neuropathic pain (p < 0.0001), neurologic deficit (p < 0.0012) and worsening of quality of life (p < 0.0002). Patients who were qualified to undergo the gabapentin treatment observed improvement in symptoms (p < 0.027), pain (p < 0.027) and neurologic deficit (p < 0.019). Quality of life did not change significantly after gabapentin treatment (p < 0.128). CONCLUSIONS: Chemotherapy substantially deteriorates the neurologic condition of the patients and the quality of life. Paclitaxel and carboplatin treated patients may benefit from gabapentin therapy in chemotherapy-induced peripheral neuropathy.

Consequences of gynecological cancer in patients and their partners from the sexual and psychological perspective.

The diagnosis of gynecological cancer and the following consequences of the treatment radically change the lives of cancer patients and their partners. Women experience negative consequences in terms of sexual, psychological and social functioning. Surgical treatment may result in a decrease in sexual pleasure and pain during intercourse. Chemotherapy and radiotherapy can cause a loss of libido and negatively affect the capacity to experience pleasure or orgasm. Treatment-related changes may include the occurrence of body image disorders, decreased quality of life as well as depressive and anxiety disorders among patients. Furthermore, a negative influence on the relationship between the affected women and their partners, as well as an adverse effect on the social activity, can be observed. Cancer is not an individual experience. It also affects partners of the sick women in terms of psychological and sexual functioning. This article depicts possible problems encountered by cancer patients and their partners from the psychological and sexual perspective. The emphasis is put on understanding sexuality not only in the context of sexual performance, but also in a wider perspective.

Chemotherapy-induced peripheral neuropathy - diagnosis, evolution and treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most frequent neurologic complications experienced by patients receiving antineoplastic drugs. Involvement of the peripheral nerves may have an important impact on daily activi-ties and lead to severe impairment of the patient's quality of life (QoL). It seems to be of crucial importance to make a correct and early diagnosis of polyneuropathy and, if possible, spare the patient unnecessary suffering or loss of function. In the preceding article we have presented epidemiology, grading and pathogenesis of the toxic CIPN. The purpose of this article is to review current knowledge of diagnostic techniques, prevention and management strategies in the context of CIPN.

The role of HE4 in differentiating benign and malignant endometrial pathology.

OBJECTIVES: The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women is being observed. More than 80% of cases is diagnosed in early stages due to early symptoms like abnormal bleeding. The remaining 20% of asymptomatic cases of endometrial cancer as well as the cases of false negative histopathological diagnoses are mostly the incidences of serous endometrial cancer and are a true diagnostic and therapeutic challenge. This was the reason of our study in which we proposed investigation of HE4 levels as a complementary diagnostic method in management and diagnosing of EC. MATERIAL AND METHODS: Serum HE4 level was measured in 92 patients with abnormal vaginal bleeding. Based on histhology after curretage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test RESULTS: The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 58.08 pmol/l. There was a significant difference between G2 and G3 endometrial cancer, and G1 and G3. (p = 0,4 and p = 0,008 respectively) Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). CONCLUSIONS: HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic and paraaortic lymphadenectomy.