[show abstract][hide abstract] ABSTRACT: Aim: The study aimed at the evaluation of the effects of radiotherapy on expression of metallothionein (MT) isoforms, both in the form of quantitative alterations in mRNA, and differences in expression of MTI/II proteins in rectal tumours.
Material for the study originated from 21 patients with rectal cancer at stage II or III. Material for immunohistochemical studies [MTI/II, Minichromosome Maintenance Protein 3 (MCM3), Ki-67] and real-time polymerase chain reaction (PCR) (mRNA of MT1F, MT1X and MT2A) was sampled twice: during rectoscopic examination before the start of the preoperative radiotherapy (samples A) and from the post operative specimen, following radiotherapy (samples B).
The level of mRNA expression for each of the studied MT isoforms was higher in cancer cells subjected to irradiation. The most extensive differences were observed for the MT2A isoforms (p=0.09). No differences were disclosed between samples A and B in expression of MT I/II protein. The material sampled after radiotherapy manifested a tendency for reduced proliferative activity of the tumour cells: the decrease of MCM3 expression was significant (p=0.022), while in the case of Ki-67, the difference approached statistical significance (p=0.096).
Application of radiotherapy to rectal adenocarcinoma cells is followed by an increase in MT mRNA expression level, affecting first of all the MT2A isoform. However, we failed to note an increased expression of MTI/II protein coded by the gene. Moreover, application of radiotherapy was followed by a decrease in expression of MCM3 protein. Our results cannot clearly confirm induction of MT after irradiation of human adenocarcinoma cells. The role of MT in radioprotection remains ambiguous.
Anticancer research 12/2012; 32(12):5291-7. · 1.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study, we hypothesized that not only endothelial malignant cells but also lymphocytes infiltrating tumor epithelium, in patients with endometrial cancer, could be an important source of the gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9) extensive production, which in turn, may facilitate tumor cells infiltration and progression due to the extracellular matrix degradation.
First, we isolated lymphocytes from the endometrial carcinoma samples taken from 41 patients who were operated on and from healthy endometrial tissue taken of the same patients after histological verification. Then, we detected the level of CD3-positive cells in endometrial tissues by flow cytometry. Simultaneously, we studied the messenger RNA expression of MMP-2 and MMP-9 in the isolated cells from malignant and unchanged endometrial tissues. Using immunohistochemistry, we compared the protein expression of MMP-2, MMP-9, and CD3 in the studied samples.
We showed the enhanced abundance of CD3 lymphocytes both by flow cytometry and immunohistochemistry in the samples from malignant tissues. The expression of MMP-9 in the endometrial carcinoma was increased significantly at the protein level but not at the messenger RNA level. We could not observe any differences concerning MMP-2 expression in both methods of detection.
CD-3 lymphocytes significantly infiltrate endometrial cancer tissue, but they do not seem to be the source of enhanced metalloproteinases 2 and 9 expression in the tumor environment. Still, owing to the immunohistochemistry staining, we could show the significant increase of MMP-9 protein in the very close vicinity of tumor-infiltrating CD3 lymphocytes. Could it be the result of CD3 lymphocyte action, or is it just the imperfection of the detecting method we used? This remains unclear. Further studies explaining the role of tumor infiltrating lymphocytes in mediating the endometrial cancer milieu are needed.
International Journal of Gynecological Cancer 09/2012; 22(8):1303-9. · 1.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cervical cancer (CC) occurs more frequently in women who are immunosuppressed, suggesting that both local and systemic immune abnormalities may be involved in the evolution of the disease. Costimulatory CD28 and inhibitory CTLA-4 molecules expressed in T cells play a key role in the balanced immune responses. There has been demonstrated a relation between CD28, CTLA-4, and IFN genes in susceptibility to CC, suggesting their importance in CC development. Therefore, we assessed the pattern of CD28 and CTLA-4 expression in T cells from PB of CC patients with advanced CC (stages III and IV according to FIGO) compared to controls. We also examined the ability of PBMCs to secrete IFN-gamma. We found lower frequencies of freshly isolated and ex vivo stimulated CD4 + CD28+ and CD8 + CD28+ T cells in CC patients than in controls. Loss of CD28 expression was more pronounced in the CD8+ T subset. Markedly increased proportions of CTLA-4+ T cells in CC patients before and after culture compared to controls were also observed. In addition, patients' T cells exhibited abnormal kinetics of surface CTLA-4 expression, with the peak at 24 h of stimulation, which was in contrast to corresponding normal T cells, revealing maximum CTLA-4 expression at 72 h of stimulation. Of note, markedly higher IFN-gamma concentrations were shown in supernatants of stimulated PBMCs from CC patients. Conclusions: Our report shows the dysregulated CD28 and CTLA-4 expression in PB T cells of CC patients, which may lead to impaired function of these lymphocytes and systemic immunosuppression related to disease progression.
Pathology & Oncology Research 11/2011; 18(2):479-89. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: To assess the incidence and risk of urinary complications after anterior rectal cancer resection with regard to the surgical device used for total mesorectal excision (TME).
During the years 2004-2009 we operated 374 rectal cancer patients with TME and the intent of autonomic nerves sparing intent. Seventeen patients underwent mesorectal dissection with ultrasound scalpel (US). They were compared to the control series of 35 cases selected from the patients for whom electrocautery was used. Selection was done in the manner to eliminate any other significant differences between groups.
Intraoperative complications, postoperative mortality, anastomotic leakage and infectious complications did not occur. Urinary bladder disturbances developed in US group in 1 patient (6%) while in 12 patients (34%) in EC group (p<0.05). In US group the character of complication was transient stress incontinence with symptoms being significantly reduced during six postoperative months. In EC group two patients had dysuria, two nycturia, one had both. Stress incontinence occurred in six patients, complete incontinence requiring catheterization in one.
When compared to EC, TME with US is related to lower risk of urinary complications and facilitates autonomic nerve preservation due to minimized thermal lateral tissue damage.
[show abstract][hide abstract] ABSTRACT: To evaluate comparatively the pain associated with ultrasound-guided core-needle (CN) and vacuum-assisted (VA) biopsy for non-palpable breast lesions.
723 women undergoing ultrasound-guided breast biopsy for BIRADS IV and V lesions according to the same standardised protocol were prospectively studied. 14-gauge CN biopsy with an automated gun was performed in 321 patients. In 402 women biopsy was made using 11-gauge VA hand-held probe. Immediately after the procedure patients were interviewed about the pain experienced during the biopsy and were asked to indicate at the pain intensity on a eleven-point scale: from 0 (none) to 10 (extreme, worst possible pain).
The median rate of pain experienced by women during biopsy was 4 (range 2-7). There were no significant differences between CN and VA groups with regard to age, body mass index, menopausal status, history of parity, hormone replacement therapy, menopausal status, breast parenchymal pattern (according to Wolfe's classification), family history of breast cancer, lesion size and number of samples. CN biopsy with an automated gun was significantly more painful (P < 0.01) than procedure with VA hand-held device as evaluated by patients: median 6 (4-7) vs 3 (2-5), respectively.
Despite using the larger needle VA procedure results in less pain experienced by women in comparison to CN biopsy with automated gun. Reduced patient discomfort should be one of the reasons for the preferential use of VA biopsy in the assessment of non-palpable breast masses.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 02/2011; 37(5):398-403. · 2.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Minimally invasive biopsy should be a standard practice in the non-operative diagnosis of breast lesions that are suspicious for or highly suggestive of malignancy. The aim of this study was to compare the procedure duration time for different methods of minimally invasive image-guided vacuum-assisted breast biopsy (VABB).
Six hundred and ninety-one women with nonpalpable breast masses classified as BI-RADS IV or V were studied. All of them underwent minimally invasive percutaneous VABB with an 11-gauge needle. In 402 patients an ultrasound-guided procedure with a hand-held device was performed while in 289 women stereotactic biopsy was carried out using a dedicated prone table unit with digital imaging. In each case the duration of biopsy was measured in terms of the total procedure time, room time and physician time.
There were no significant differences between the stereotactic and ultrasound-guided groups with regard to patient age, body mass index, menopausal status, history of parity, hormone replacement therapy, breast parenchymal pattern (according to Wolfe's classification), family history of breast cancer, mass size and number of samples. Ultrasound-guided biopsy was found to take significantly less time than prone stereotactic biopsy in every aspect of procedure duration. Mean total procedure time, room time, and physician time in minutes were 26.7 ± 8.2 vs 47.5 ± 9.4 (P <0.01), 23.1 ± 8.5 vs 36.5 ± 9.2 (P <0.05), and 12.3 ± 5.6 vs 18.6 ± 5.9 (P <0.05), respectively.
Ultrasound-guided breast biopsy is less time-consuming than the stereotactic procedure for both the patient and the physician. Because of the shorter procedure time (as well as other well-known advantages: real-time imaging, lower cost), ultrasound-guided biopsy should be considered the method of choice for sampling suspicious nonpalpable breast masses.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to compare the imaging symptoms and microscopic findings in females with lobular neoplasia (LN) found on biopsy. 1,478 women who underwent primary open biopsy or surgical excision after percutaneous biopsy were reviewed. In 24 of them (1.6%), LN was found. In four patients, excisional biopsy with hook-wire localization was done primarily due to the radial scar. In 20 females, surgical excision of BIRADS 4 lesion was performed because of the presence of LN in specimens from the vacuum-assisted or core-needle percutaneous biopsy. Postoperative pathologic findings were compared to the radiological symptoms. In 13 women, LN did not produce any radiological symptoms and was an additional histologic finding existing near the other lesion: fibroadenoma and radial scar. In none of these lesions was an invasive cancer noticed. In one single patient, ductal carcinoma in situ was observed in the other segment of the breast. Invasive ductal cancer developed in the contralateral breast in one patient. In 11 patients, LN was diagnosed due to radiological symptoms produced by itself. In this group, the invasive lobular cancer was found in seven lesions (64%). Our finding suggests that LN producing suspicious radiological symptoms can be a different biologic type of this lesion when compared asymptomatic LN diagnosed which is usually found on biopsy as additional microscopic pathology. Symptomatic LN is probably associated with a higher potential of malignant transformation.
Folia Histochemica et Cytobiologica 01/2011; 49(3):417-24. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
Hepatocyte growth factor plays an important role in tumor growth, metastasis and angiogenesis. C-met is HGF's high affinity receptor.AimThe aim of the study was to assess the correlations between c-met expression and clinic-pathological factors in breast cancer tissues. Furthermore, the purpose of the study was to evaluate the prognostic value of the hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients.Materials and methodsTumor samples were collected from 302 patients with breast carcinoma treated with primary surgery. We have assessed the percentage of tumor cells with c-met expression, the intensity of reaction and the ratio of these two factors—immunoreactivity according to the Remmele score.ResultsWe have observed no correlations between HGFR immunoreactivities and clinical parameters (tumor size, grade, axillary lymph node status, age). In 5-year observation we have found prognostic value of assessing c-met immunoreactivity in primary tumor.Conclusion
Our study has revealed prognostic value of c-met. Unlike in other authors’ studies, our patients’ group is very homogenous which might contribute to obtained results.
Reports of Practical Oncology and Radiotherapy 01/2011; 16(5):173–177.
[show abstract][hide abstract] ABSTRACT: YKL-40 is detected in the early nineties not only a glycoprotein secreted by cancer cells, but also of neutrophils, chondrocytes and endothelial cells. Biological function of YKL-40 are not exactly known, it is suggested that this protein participates in many physiological and pathological processes such as proliferation, angiogenesis, mitogenesis and remodelling. It is also a factor antyapoptotic and growth factor for some cells. Increased levels of YKL-40 in serum have been described in many diseases running with inflammation such as rheumatoid arthritis, systemic lupus erythematosus and Crohn's disease, and also in the group of cardiovascular diseases. Determination of the concentration of serum YKL-40 was also used in oncology. The tumors at various sites were found elevated levels of this marker in serum, as well as overexpression in tumor tissue. It was observed that higher titers YKL-40 levels are associated with shorter overall survival and disease-free period. It is suggested that measuring the concentration of YKL-40 in serum and its expression in tumor tissues may serve as a valuable and independent prognostic factor.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 06/2010; 28(168):505-8.
[show abstract][hide abstract] ABSTRACT: The aim of the study was to evaluate the prognostic value of the vascular endothelial growth factor A (VEGF-A) and hepatocyte growth factor receptor (HGFR, c-met) expressions in homogenous group of breast cancer patients. Tumor samples were collected from 98 patients with invasive ductal breast carcinoma stage II treated with primary surgery. We have observed a strong correlation between VEGF-A and c-met. No correlations were found between VEGF-A or HGFR expressions and clinical parameters (tumor size, grade, axillary lymph node status, age), 5- and 10-years DFS or OS. Our study did not reveal any prognostic value of c-met or VEGF. In addition they are not useful to separate a patients' subgroup with poor prognosis. Unlike in other authors' studies, our patients' group is very homogenous which might tribute to obtained results.
Folia Histochemica et Cytobiologica 01/2010; 48(1):78-83. · 1.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Niska resekcja przednia raka odbytnicy z zaoszczędzeniem nerwów autonomicznych z użyciem noża ultradźwiękowego – wstępne obserwacje wyników czynnościowych 1 2 nd Abstract Background. Achieving effective local control and obtaining optimal functional outcomes are now both needed in the surgical management for rectal cancer. Objectives. The aim of this study was to assess early functional results after low anterior resection performed with an ultrasound scalpel. Material and Methods. Nineteen consecutive rectal cancer patients surgically treated during the years 2004–2008 with low anterior resection with sharp total mesorectal excision were studied. Dissection was performed with an ultrasound scalpel instead of electrocautery. The frequency of axial vibration and the extension of longitudinal vibration were 55.5 kHz and 75 µm, respectively. Special effort was made to identify and preserve autonomic nerves. Postoperative complications and functional results were analyzed. Results. Surgery was completed with no intraoperative complications. The mean operating time was 150.20 ± 27.09 min. In each case, resection and anastomosis (straight, double-stapled) were done with ease. There was no post-operative mortality. Blood transfusion was not required. Neither anastomotic leakage nor abdominal infectious complications were noticed. Delayed wound healing and prolonged bowel paralysis occurred in two patients (13%) with diabetes and chronic obturative pulmonary disease, respectively. Urinary bladder disturbance developed in one female patient (7%) as stress incontinence. This dysfunction was transient, with symptoms being significantly reduced during the six postoperative months. Conclusions. Based on this initial series, rectal dissection with an ultrasonic knife appears safe and seems to facili-tate autonomic nerve preservation, probably due to minimized thermal damage to tissue. Further investigations and cost-effectiveness analysis are needed to assess its usefulness for the routine surgical practice (Adv Clin Exp Med 2010, 19, 1, 113–119).
[show abstract][hide abstract] ABSTRACT: Abnormal expressions of the costimulatory molecules CD28, "inducible co-stimulator" (ICOS), and inhibitory molecule cytotoxic T-lymphocyte antigen-4 (CTLA-4) lead to disturbances of immune response and entail an increased risk of cancer. This study was undertaken to evaluate the association between the polymorphisms CTLA-4c.49A>G, CTLA-4g.319C>T, CTLA-4g.*642AT(8_33), CTLA-4g.*6230G>A (CT60), CD28c.17+3T>C, and ICOSc.1554+4GT(8_15), and susceptibility to CSCC. The association between CTLA-4g.319C>T[T] allele and [TT+CT] genotype and susceptibility to CSCC was observed (OR = 1.99, p = 0.003, and OR = 2.07, p = 0.005, respectively). The CTLA-4g.319C>T[T] allele and [TT+CT] genotype increased the risk of well-differentiated CSCC by a factor of 3.84 and 4.44 (p = 0.00001, and p = 0.00001, respectively). In patients with moderately differentiated CSCC, a trend toward increased frequency of CTLA-4g.319C>T[T] allele and CTLA-4g.319C>T[TT+CT] genotype was noticed (OR = 1.68, p = 0.09, and OR = 1.75, p = 0.09, respectively), whereas in low differentiated CSCC such relation was not observed. Both CTLA-4g.*642AT(8_33) [(AT)(8)]/[(AT)(8)] homozygote and [(AT)(8)] allele were overrepresented in CSCC patients in comparison with healthy women (p = 0.004, OR = 1.93, and p = 0.03, OR = 1.41, respectively) but this polymorphism was not related to histologic grade of tumor. CD28c.17+3T>C polymorphism was not associated with susceptibility to CSCC in whole group of patients, but CD28c.17+3T>C[C] allele and CD28c.17+3T>C[CC+TC] genotype were more frequently observed among well differentiated CSCC patients compared with controls (OR = 1.89, p = 0.05, and OR = 2.05, p = 0.05, respectively). Other studied polymorphisms were not associated with susceptibility to CSCC and with histologic grade of CSCC. Our results suggest that the CTLA-4 gene is susceptibility gene to CSCC especially to well-differentiated tumor, while association between CD28 gene polymorphism and disease is restricted only to the well-differentiated CSCC.
Human immunology 11/2009; 71(2):195-200. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: To evaluate the access to axilla, postoperative complications, and cosmetic results of the modified radical mastectomy with a Y-shaped approach especially designed for women with obesity.
One hundred seventeen consecutive women with obesity with infiltrating breast cancer were studied. All of them were not eligible for breast-conserving therapy and underwent modified radical mastectomy. Operation was performed using a surgical technique designed to improve the axillary clearance and to eliminate the lateral dog ear deformity. Two oblique incisions were added to the traditional transverse Stewart incision at the lateral part forming the Y-shaped approach. After lateral flap retraction, the axillary dissection was done. Before closing the wound, the triangular flap was advanced medially, whereas superior and inferior areas of redundant skin overlying the latissimus dorsi muscle were excised.
No intraoperative complications were observed. In each case, the axillary dissection (with level 3 node clearance when needed) was performed with ease. The wound was healed by primary adhesion, giving an excellent cosmetic result without lateral dog ear deformity. Skin flap necrosis was found in 2 elderly patients. Wound hematoma and surgical site infection developed in 1 patient each. Necrosis of the apex of axillary triangle occurred in one woman with diabetes. These rare complications were managed successfully in all the cases.
The Y-shaped approach for modified radical mastectomy is a simple and safe technique. It facilitates the wide access to axilla and improves cosmesis in women with obesity by eliminating lateral dog ear deformity.
International Journal of Gynecological Cancer 11/2009; 19(8):1454-8. · 1.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Available evidence suggests that vascular endothelial growth factor (VEGF) a potent regulator of vasculogenesis and tumor angiogenesis may be a predictor of recurrence in breast cancer patients. We sought to determine whether VEGF serum levels (VEGF-A, VEGF-C and VEGF-D) in 377 patients with malignant and benign breast tumors differ and whether there is association between vascular growth factors, clinicopathologic features and prognosis. There was no significant difference in investigated circulating angiogenic markers between patients with malignant and non malignant lesions. We found strong correlation between VEGF-A and VEGF-D and between VEGF- C and VEGF-D. Besides serum VEGF-D levels and estrogen receptor (ER) expressions no other correlations between VEGF and clinicopathologic variables were observed. However, elevated VEGF-A and VEGF-C concentrations were associated with increased number of erythrocytes, leukocytes and platelets. In Cox model values of angiogenic serum markers and recognized prognostic markers in breast cancer, VEGF-C turned out as independent prognostic factor. Our study is the first analysis showing correlation between serum concentrations of three angiogenic factors: VEGF-A, VEGF-C, VEGF-D. Associations between angiogenic cytokines and number of blood cells may be due to release of VEGF from platelets and leucocytes. Prognostic role of VEGF is still uncertain, though VEGF-C has a potential to serve as a prognostic marker.
Pathology & Oncology Research 10/2009; 16(3):337-44. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: For rectal cancer patients without nodal metastases the identification of unfavourable factors can be helpful for the better selection for adjuvant therapy and multimodality treatment. The aim of this study was to evaluate the impact of clinico-histological parameters on prognosis in node-negative rectal cancer patients. One hundred and thirty-nine consecutive node negative rectal cancer patients with complete five-year follow-up were studied prospectively. All of them underwent curative anterior resection with total mesorectal excision technique. Seventy-eight patients with tumour penetration beyond the bowel wall received neo-adjuvant short-course radiation (25 Gy) followed by surgery within 1 week and postoperative chemotherapy with 5-fluorouracil and folinic acid in six cycles or adjuvant radiochemotherapy: irradiation (50.4 Gy) combined with chemotherapy (as above). Cancer-specific survival was calculated according to the Kaplan-Meier method. Variables significant in univariate analysis by log-rank test (P < 0.05) entered the Cox proportional hazard model. Survival was decreased for males, older patients (>60 years) with extraperitoneal, poorly differentiated cancers, tumours with mucinous histology and with the absence of lymphocytic infiltration but with the lack of statistical importance. Prognosis was significantly improved for patients with T2 tumours versus T3 (P < 0.01) and with cancers with expanding growth comparing to diffusely infiltrating ones (P < 0.01). In multivariate analysis these parameters significantly and independently influenced survival (P < 0.01 and P < 0.05, respectively). Diffusely infiltrating growth of tumour can reflect the more aggressive cancer behaviour and unfavourable course of disease despite the optimised local control. Apart from the extent of tumour penetration the type of invasive margin can be an additional parameter helpful for the optimal treatment planning and better patient selection for postoperative chemotherapy.
Pathology & Oncology Research 09/2009; 16(2):201-6. · 1.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study was to assess the prognostic role of CD4 and CD8 expression and the type, density, localization and distribution of tumor infiltrating lymphocytes (TILs) in patients with breast cancer.
Tissue samples were obtained from 88 breast cancer patients with operable disease and ductal histology. Forty-three women had pathologically confirmed axillary lymph node involvement. The TILs and expression of CD8 (cytotoxic T-cells) and CD4 (T-helper cells) were evaluated in the tumor samples using mouse monoclonal antibodies.
Thirteen patients relapsed; nine of them had strong expression of CD4 and CD8, which was statistically significant. The patients with high expression of CD4 or CD8 had distinctly worse cancer specific overall survival (OS). High correlations between CD4 and CD8 expression and lymph node status and intensity of lymphatic infiltrate as well as between both markers were found.
The analysis of tumor-infiltrating immune cells may be a valuable prognostic tool and a marker of lymph node involvement.
Anticancer research 08/2009; 29(7):2445-51. · 1.71 Impact Factor