Introduction: Among the HPV infection risk factors one can list: age, early sexual activity, frequent change of sexual partners, multiparity, low socioeconomical status, coexistence of Chlamydia trachomatis, HSV type 2, HIV infections, vitamin deficiencies, smoking cigarettes, using hormonal contraceptives, immune system disorders and also pregnancy. The aim of the study is the assessment of human papillomavirus infection frequency in the course of pregnancy, particularly with attention to HPV type 16 infection. Material and methods: The study included 242 pregnant women who in the years 2004-2008 were treated in the Pathology of the Pregnancy Ward and Gynecologic-Obstetric Outpatient Clinic in the Voivodal Brodnowski Hospital. The patients included to the study had had cervical smear test performed by PCR method for HPV. Results: In the examined group of 242 pregnant patients human papillomavirus was isolated from 150 (62%) patients. Type 16 was stated in 87 (58%) patients. In case of normal pregnancy the presence of HPV virus was stated in 70.8% of cases (51 out of 72 women). In this group HPV type 16 comprised 61.6%. In pregnancies complicated with the symptoms of early termination the infections were stated in 99 out of 170 patients (58.2%). HPV type 16 infection was stated in 92.9% of cases. Conclusions: 1) In the analyzed material the frequency of human papillomavirus infection equaled 62%. Type 16 of virus caused 58% of these infections. 2) Regardless of the age of pregnancy and its course the percentage of cervix infections by HPV type 16 was quite significant and oscillated from 36% to 65%. 3) In patients who lost their pregnancies before 22 week of gestation, HPV type 16 was significantly more frequently isolated from miscarried tissues in comparison to its presence in cervical canal smear.
Neoplastic markers represent high molecular weight substances produced both by neoplastic and healthy cells in response to a developing tumor. A marker may also involve any assayable substance in tumor tissue which manifests immunoreactivity distinct from that in normal tissues. Neoplastic markers serve in the detection of the disease, monitoring of treatment efficacy and in the detection of a relapse. In the case of ovarian cancer, the most recognizable marker involves CA-125, an elevated level of which is detected in around 80% serous carcinomas and which increases as the disease progresses. Early stages of ovarian carcinomas are detected by estimation of HE4 (human epididymis protein). The Risk of Malignancy Index (RMI algorithm) is based on the estimation of the CA-125 level, transvaginal ultrasound examination and condition of menopause. Other algorithms used in ovarian carcinoma include OVA-1, based also on CA-125 level, menopausal status and on four proteomic markers, and ROMA (Risk of Ovarian Malignancy Algorithm), based on CA-125 and HE4. Other markers of less pronounced importance for ovarian carcinoma include:
– CA-19-9 (antigen of gastrointestinal carcinoma) – of particular use in carcinomas of gastrointestinal tract, including pancreatic carcinoma but also mucous ovarian carcinoma;
– CEA (carcinoembryonic antigen) – a marker of alimentary tract carcinomas, including colorectal carcinoma, gastric carcinoma but also mucous ovarian carcinoma;
– CA-15-3 (MUC1) – the recognized marker of breast carcinoma, the concentration of which increases in advanced stages of ovarian carcinoma;
– YKL-40 (glycoprotein of human cartilage) – allowing detection of early stages of ovarian carcinoma and its relapses;
– kisspeptin (KiSS-1) – associated with the inhibition of metastases in clarocellular ovarian carcinoma;
– HIF-1α (hypoxia-inducible factor-1α) – similarly to clusterin, linked to resistance to chemotherapy;
– E-cadherin, SDF-1 and metadherin linked to the development of metastases;
– enzymatic markers COX-1 and in particular COX-2 correlate with the progress of the disease while an increased COX-2 level indicates resistance to chemotherapy.
The results of malignant cancer treatment are still unsatisfactory that is why new medications are intensively being searched. We currently expect that cytostatic drugs will actively destroy not only cancer in the site of its origin but also metastatic foci. New generation drugs should actively act on neoplastic tumors which have so far been thought to be chemoresistant and prevent the spread of the disease. The search for new, more efficient cytostatic drugs causes that the studies are also conducted basing on the related groups of well-known and already used in cancer treatment chemical elements. Platinum is such an element and its “relative” ruthenium fascinated scientists with its chemical possibilities. Ruthenium has the properties of the minerals from the group of transition metals of the group 8. It is a solid metal of good conductivity. The studies on ruthenium as a compound potentially destroying cancer cells indicate that it influences cell apoptosis binding to the cell membrane protein similarly as iron binds to transferrin – it enters the cells in this way. Its activity is related to the activation of the compound Ru(III) into the form Ru(II), then it acts on DNA of the cells which is performed particularly actively in poorly oxygenated environment such as the interior of a cancer. Moreover, ruthenium compounds increase the adhesion of cancer cells making their migration and formation of metastases difficult.
The paper is an overview of metal-containing compounds, i.e. platinum derivatives, used to create extremely active oncologic drugs. Platinum derivatives are in use for about 40 years in the treatment of most (nearly 80%) malignant tumors. Among metal-containing drugs, platinum derivatives are longest in use; they are very active tumor-destroying agents, have a potent antitumor effect and are the basis of several multidrug protocols. Unfortunately, apart of their antitumor effect, cisplatin has also considerable toxicity manifesting in many organ systems. Second- and third-generation platinum derivatives are being developed, aiming at reduction of these unfavorable effects while preserving or even enhancing its antitumor activity. In order to reduce platinum-related toxicity, such modalities as cytoprotection, pharmacogenetics and molecular biology are resorted to, aiming at isolation of active genes participating in the development of drug resistance. The aim of cytoprotection is to protect and strengthen normal tissues against deleterious impact of chemotherapy by rapid regeneration of healthy tissue, with no reduction of activity of cytostatic drugs. Pharmacogenetics aims at discovery of genes, their interactions and responses to particular cytostatic agents used in oncology. The goal is to point-out patients most at risk of developing unacceptable toxicity, even before application of the drug. History of use of cisplatin in the treatment of tumors indicates that improvement of treatment outcomes is the sum-total of inputs of interdisciplinary teams: chemists, biologists and oncologists.
Worldwide, cervical cancer is the second most common genital malignancy in the females. Estimated number of women affected therewith reaches 1.4 million. In Poland, cervical cancer is the fourth most common cancer, preceded by breast cancer, lung cancer and endometrial cancer, and the fifth most common cause of cancer-related mortality. Cervical cancer usually affects women aged 45-59. Current standards of treatment of cervical cancer include surgery (still the basic modality at stages 0, IA, IB and IIA), radiotherapy, chemotherapy and radiochemotherapy, which are implemented at stages IB-IVB. Surgical treatment of cervical cancer patients is classified as follows: primary treatment, treatment of coexisting genital conditions prior to planned radiochemotherapy, treatment of recurrent cervical cancer and palliative treatment. Low efficacy of radiotherapy and chemotherapy as the sole treatment modalities in cervical cancer resulted in increased interest in radiochemotherapy, i.e. a technique combining radiation with cytotoxic drugs. Randomized trials revealed an improvement of 3-years’ survival by 10-18% and the drug used most often was cisplatin administered alone or combined with a 96-hours’ infusion of fluorouracil. Cervical cancer is currently considered one of the tumors, where multimodal treatment is a therapeutic standard.
An interesting field of research in tumor immunology are T-lymphocytes and NK-cells in the area directly adjacent to tumor, i.e. tumor-infiltrating lymphocytes (TIL). An important indicator of immune control of cancer cells is the correlation between intensity of TIL infiltrate and clinical course of the disease. The aim of this paper is a review of particular types of immunocompetent cell infiltrating the tumor and a review of English literature as to data concerning prognostic significance of TIL subpopulations in ovarian, endometrial, cervical and vulvar cancer. Material and method: The PubMed database was searched using key words: CD8+, CD4+, FOXP3+, CD57+, CD56+, NK, combined with phrases: cervical cancer, vulvar cancer, ovarian cancer, endometrial cancer and prognosis. Results: Most important TILs include cytotoxic T-lymphocytes, mostly represented by the CD8+ population, helper T-lymphocytes, designed as CD4+ cells, regulatory lymphocytes Treg, where the most specific maker is transcription regulator forkhead box P3 (FOXP3), and NK/NKT cells (natural killer/natural killer T-lymphocytes), identified by CD56 and CD57. A close correlation was found between patients’ survival and intensity of infiltrate by CD8+ cells and indicators CD8+/FOXP3+, CD8+/CD4+ and ovarian cancer, endometrial cancer and cervical cancer. An exception to this is vulvar cancer, where CD8+, CD4+ and FOXP3+ have no prognostic significance. Conclusions: Severity of local cytolysis of tumors and inhibition of immunosuppressive activity of regulator cells may be used in future therapeutic strategies in patients with ovarian, endometrial and cervical cancer. In vulvar cancer we should rather focus on non-specific immune response for tumor control.
Uterine papillary serous carcinoma (UPSC) is an extremely malignant tumor associated with a grim prognosis. It accounts for less than 10% of all cases of endometrial cancer. Mean age at presentation is 68 years. Morphological appearance is similar to poorly differentiated serous cancer of the ovary. A characteristic feature is extensive invasion of blood and lymph vessels and rapid intraperitoneal dissemination. Endometrial glandular dysplasia is currently considered a precursor lesion of UPSC. The basic pathogenetic event is mutation of suppressor gene TP53 and overexpression of HER2/neu (human epithelial growth factor receptor 2). UPSC differs morphologically, genetically and clinically from endometrioid cancer. It is usually diagnosed in slender elderly women and is not correlated with hormonal risk factors. The serous type, in contrast to endometrioid cancer (EEC) usually developing within atypical proliferative lesion, develops mainly within atrophic endometrium, is characterized by high grade of malignancy (G3) and aggressive clinical course. Metastases within the abdominal cavity and lymph nodes develop rapidly and recurrences are usually distant and multifocal. Every case of endometrial cancer of any grade, with a component of serous cancer, should be treated like serous cancer of the ovary. Properly performed staging includes: hysterectomy with adnexectomy, pelvic and periaortal lymphadenectomy, omentectomy and inspection of the peritoneal cavity, as in the case of ovarian cancer. Adjuvant treatment includes chemotherapy based on platinum and taxane with or without radiotherapy. High frequency of extrauterine serous foci even at early stages of the disease necessitates an aggressive and multimodal therapeutic approach. Unfavorable treatment outcomes in UPSC reported to date, force us to search for novel therapeutic techniques, based mainly on targeted therapies.
Low-grade lymphomas pose a considerable therapeutic problem, as they yield to treatment very reluctantly. Not infrequently we are faced with resistance to chemotherapy. This type of lymphomas are usually seen in persons of middle or advanced age, rarely in people under 30. Due to the presence of CD20+ receptor on cell membranes of lymphoma originating from B-cells, monoclonal antibody anti-CD20+ (rituximab) has been introduced to the therapy. This has certainly resulted in improved outcomes. Of value in consolidation treatment of low-grade lymphomas is also autologous or allogenic hematopoietic cell transplantation (autoHSCT, alloHSCT). As escalation of dose of cytostatics as myeloablative treatment prior to autoHSCT or alloHSCT may not guarantee total eradication of residual lymphoma cells, research focuses on treatment modalities which might improve late outcomes in this tumor type. In this setting useful proved radioimmunotherapy with 90Y-ibritumomab tiuxetan (Zevalin). Zevalin combined with high-dose chemotherapy can be used now as a component of myeloablative treatment prior to autoHSCT. Reduced intensity conditioning (RIC) contributes to reduced mortality associated with standard conditioning protocol administered prior to transplantation, but may facilitate disease recurrence. Radioimmunotherapy using ibritumomab may reduce recurrence rate and, as a conditioning measure, may be initiated on the outpatient setting, prior to admission to bone marrow transplantation center. Labeling of antibodies and their application must take place at a Nuclear Medicine Unit, observing all necessary precautions and regulations concerning radiation protection. Administration of ibritumomab is preceded by application of two doses of rituximab: 250 mg/m2, 7 days and 4 hours prior to the RIT procedure. The dose of rituximab administered one week before, according to recommended protocol of ibritumomab use, initially preceded dosimetry (administration of indium-labeled antibodies).