Amplification and co-regulators of androgen receptor gene in prostate cancer.

Prostate cancer is the second most common malignancy among males after lung cancer. The growth of prostate cancer cells depends on the presence of androgens, a group of steroid hormones that include testosterone and its more active metabolite dihydrotestoste-rone. Most prostate cancers are androgen-dependent and respond to the antiandrogens or androgen-deprivation therapy. However, the progression to an androgen-independent stage occurs frequently. Possible mechanisms that could be involved in the development of hormone resistant prostate cancer causes including androgen receptor (AR) mutations, AR amplification/over expression, interaction between AR and other growth factors, and enhanced signaling in a ligand-independent manner are discussed.

Shaken baby syndrome: intending to harm or attempting to help?

PURPOSE: To describe the role of ophthalmologists in shaken baby syndrome evaluation. METHODS: Case report. RESULTS: A 3.5-month-old girl was admitted to the Pediatrics Clinic with lethargy. The mother, who brought in the baby, claimed that the baby had fallen from her cradle 6 hours ago. Clinical examination showed signs of head injury. Ophthalmologic examination was requested and revealed extensive retinal hemorrhages bilaterally covering the whole fundus, and retrohyaloid hematoma in the right eye. Computerized tomography neuroimaging documented large subdural hematomas exerting force on the brain parenchyma. The sum of the results of the clinical and neuroimaging examination-retinal hemorrhages and subdural hematomas-was indicative of violent shaking of the baby. Coronal evaluation was unable to determine whether the baby was abused by her parents or whether she was accidentally hurt. CONCLUSIONS: Ophthalmologic examination is necessary to document shaken baby syndrome since it reveals the retinal hemorrhages which together with the neuroimaging findings are almost always present in such cases. However, even when all the signs of shaken baby syndrome are present, it is difficult and sometimes destructive for a parent to be falsely accused of abusing his or her own child.

Acute septic cholelithiasic cholecystitis and adenocarcinoma of the gallbladder; an interesting association.

BACKGROUND AND STUDY AIMS: Primary carcinoma of the gallbladder may present as acute lithiasic cholecystitis that leads to severe septic complications. The correlation between severe sepsis of the gallbladder and primary carcinoma is unclear. The goal of the present study is to examine the relation between severe septic complications of lithiasic cholecystitis and primary carcinoma of the gallbladder. PATIENTS AND METHODS: A group of 72 patients (22 males, 50 females, age range: 45-99, mean age: 68.6 years), with severe septic cholelithiasic cholecystitis was treated with emergency surgery after failure of conservative treatment, and patients found with primary carcinoma of the gallbladder were registered. The resectability and operability of the tumor were studied, as well as tumor staging and overall patient survival. RESULTS: During urgent surgery for severe septic lithiasic cholecystitis, 12 patients (12/72, 16.6%) were found with gallbladder carcinoma. Patients with septic acute lithiasic cholecystitis and carcinoma had a higher mean age compared to those without carcinoma (74.8 vs. 67.4 yrs). Eleven of 12 (91.6%) carcinomas were inoperable, despite resectability of 8 out of 12 (66.6%), and overall patient survival was limited to a few months after surgery. CONCLUSIONS: Severe septic complications in elderly patients with a long-standing history of gallbladder stones may co-exist with primary carcinoma of the gallbladder. The percentage of a gallbladder carcinoma detected in septic patients reaches up to 16.6%. Even if these patients have a poor general health, surgical intervention is a solution when they appear with severe septic clinical symptoms caused by gallstones or carcinoma, in order to avoid lethal sepsis. The possibility of a carcinoma hidden in the gallbladder must be in mind during surgery. Imaging studies before surgery may detect the carcinoma; in most cases carcinomas are inoperable, although colecystectomy may be performed during surgery.

Thoracoabdominal wall tumour seeding after percutaneous radiofrequency ablation for recurrent colorectal liver metastatic lesion: a case report with a brief literature review.

Radiofrequency is a safe and effective minimally invasive procedure in the treatment of liver and other organs neoplastic lesions. Percutaneous access of neoplastic liver tissue is the most common access and electrodes are placed with imaging guidance into the tumour to be ablated. Complications during and after radiofrequency ablation (RFA) are of major or minor severity. Tumour dissemination related to the percutaneous access seems to be very unusual. Herein, we present a rare case of thoracoabdominal tumour wall dissemination after RFA of a recurrent hepatic colorectal metastasis previously removed by surgery. A 64-year-old man with a recurrent hepatic metastatic lesion was treated with internally cooled radiofrequency (RF) for ablation of a 3x3 cm in size tumour mass. Two sessions of RFA in one-month period were performed. Computed tomography (CT) of the upper abdomen and carcinoembryonic (CEA) antigen were used for estimation of the disease progression in the patient's follow-up. Ten months after RFA the patient presented abdominal pain and a mass appeared on the right thoracoabdominal area with simultaneous lung metastases. In conclusion, a large size, bulky and superficial mass on the liver parenchyma adjacent to the thoracoabdominal wall as well as multiple RFA sessions, seem to represent risk factors for tumour dissemination through the needle electrode used during the RFA procedure in hepatic metastases of colorectal cancer.

Molecular profiling and genomic microarrays in prostate cancer.

In the present review article a global approach regarding the usefulness of genomic microarrays in prostate cancer management, is attempted. Cancer is a multistep process of mutations in key regulatory genes and epigenetic alterations that result in loss of balanced gene expression. A complete knowledge of the interaction between the genetic variability of the neoformation (tumor profiling) and the genetic variability of the host (inherited genome profiling), will be able to determine the better strategy against the cancer and the less toxicity for the patient. Alterations in the sequence of the hormone binding domain of the androgen receptor as well as mutations in some genes, determine radioresistance and resistance or sensitivity to some chemotherapeutic drugs. New therapies using monoclonal antibodies directed against specific extracellular binding domains of some receptors are based on molecular alterations observed in tumors.

In breast carcinoma dysadherin expression is correlated with invasiveness but not with E-cadherin.

Reduction/loss of E-cadherin is associated with the development and progression of many epithelial tumours. Dysadherin, recently characterised by members of our research team, has an anti-cell-cell adhesion function and downregulates E-cadherin in a post-transcriptional manner. The aim of the present study was to study the role of dysadherin in breast cancer progression, in association with the E-cadherin expression and the histological type. We have selected ductal carcinoma, which is by far the most common type and lobular carcinoma, which has a distinctive microscopic appearance. Dysadherin and E-cadherin expression was examined immunohistochemically in 70 invasive ductal carcinomas, no special type (NST), and 30 invasive lobular carcinomas, with their adjacent in situ components. In ductal as well as in lobular carcinoma dysadherin was expressed only in the invasive and not in the in situ component, and this expression was independent of the E-cadherin expression. Specifically, all 10 (100%) Grade 1, 37 out of 45(82.2%) Grade 2 and six out of 15 (40%) Grade 3 invasive ductal carcinomas showed preserved E-cadherin expression, while 'positive dysadherin expression' was found in six out of 10 (60%) Grade 1, 34 out of 45(75.5%) Grade 2 and all 15 (100%) Grade 3 neoplasms. None of the 30 infiltrating lobular carcinomas showed preserved E-cadherin expression, while all the 30 infiltrating lobular carcinomas exhibited 'positive dysadherin expression'. Dysadherin may play an important role in breast cancer progression by promoting invasion and, particularly in lobular carcinomas, it might also be used as a marker of invasion.

E-cadherin adhesion molecule and syndecan-1 expression in various thyroid pathologies.

UNLABELLED: Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion is likely to constitute one of the main factors leading to the reduced cell-cell and cell-matrix adhesion characteristics of tumor cells and play a pivotal role in the acquisition of invasive and metastatic proprieties by neoplastic epithelial cells. AIM: To elucidate the role and alterations of syndecan-1 expression in comparison with those of E-cadherin in normal and pathological thyroid glands (TG). METHODS: A total of 55 TG carcinomas, 40 TG adenomas, 40 cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples, were evaluated by immunohistochemistry. The staining intensity, and localization of syndecan-1 and E-cadherin in sequential sections were examined, and semi-quantified. RESULTS: Immunostaining of syndecan-1 and E-cadherin was strong in normal follicular TG epithelial cells, and located mainly in basolateral membrane. No significant change was seen in either molecule in hyperplastic TG disorders compared with TG adenomas. A significant reduction in expression of both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively). Similarly, there was a significant reduction of both molecules expression in poorly differentiated and anaplastic TG carcinomas compared to well differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075). CONCLUSION: Decreased E-cadherin and syndecan-1 expression along with decreasing cellular differentiation may be involved in the complex mechanism of progression of TG pathology.

Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA.

Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t-test was used and P-values <0.001 were regarded as statistically significant. Serum Se was 42.5+/-7.5 microg l(-1) in breast cancer patients and 67.6+/-5.36 microg l(-1) in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10+/-1.7 U ml(-1) (normal <2.5 U ml(-1) in nonsmokers/<3.5 U ml(-1) in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied (P<0.001). Neoplastic tissue Se concentration was 2,660+/-210 mg g(-1) tissue; its concentration in the adjacent non-neoplastic tissue was 680+/-110 mg g(-1) tissue (P<0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied (r=-0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process.

Intravitreal dirofilariasis: a rare ocular infection.

Human ocular dirofilariasis is a zoonotic disease, rare in Europe, caused by filarial nematodes. The parasite is either encysted in a subcutaneous nodule or located under the bulbar conjunctiva. We report the case of a 62-year-old man with intravitreal dirofilariasis, which is a rare site of presentation of the nematode in the human eye. It was located in the fundus area and was surgically removed. The nematode was identified as Dirofilaria repens (D. conjuctiva) by two different Microbiology Departments, making this the fifth report of identified intravitreal dirofilariasis caused by D. repens in the relative literature.

Expression of matrix metalloproteinase-9 (gelatinase B) in benign, premalignant and malignant laryngeal lesions.

The matrix metalloproteinases (MMPs) are a family of proteolytic zinc-containing enzymes, which are responsible for the breakdown of the extracellular matrix components in pathological and physiological conditions. They are involved in basement membrane disruption, stroma and blood vessel penetration, metastasis and more recently there is evidence that they participate in tumor growth and angiogenic events. Matrix metalloproteinase 2 and 9 (MMP 2 and 9) belong to the gelatinases, a subgroup of MMPs, and have the capacity to degrade the triple helix type IV collagen of basal lamina of the basement membrane. With the present study, we tried to demonstrate the expression of MMP-9 immunohistochemically, comparatively in benign, premalignant and malignant lesions of the larynx. We studied 154 laryngeal lesions including 55 squamous cell carcinomas, 8 in situ carcinomas, 54 cases of dysplasia (of low and intermediate grade), 13 papillomas and 24 cases of keratosis. Overexpression of MMP 9 was observed in 74.4% and 50% in invasive and in situ squamous cell carcinomas respectively. In dysplastic cases, in papillomas and in keratoses the percentage of overexpression was 62.9%, 61.53% and 54.16% respectively and the expression of MMP-9 was significantly higher in invasive squamous cell carcinomas compared to dysplasias (p=0.000004). Also significantly higher was the expression of MMP-9 in dysplastic cases compared to papillomas (p=0.023). The MMP-9 expression was related neither to survival nor to the other available clinicopathological parameters (tumor size, grade, clinical stage, lymph node status and patient age). In conclusion, our study indicates that the expression of MMP-9 is up-regulated in a stepwise fashion, with two main steps, the first one, when a dysplastic lesion evolves and the next one, when the dysplasia progresses to invasive carcinoma.

Involvement of dysadherin and E-cadherin in the development of testicular tumours.

Testicular neoplasms are comprised of a variety of histologically different forms, and their pathogenesis has not been elucidated. Dysadherin is a recently described cell membrane glycoprotein, which has an anticell-cell adhesion function and downregulates E-cadherin. In this study, we examined immunohistochemically the expression of E-cadherin and dysadherin in 120 testicular neoplasms (37 seminomas-26 classic, five spermatocytic and six anaplastic-, 45 embryonal carcinomas, 10 mixed germ cell tumours, two yolk sac tumours, 10 mature and eight immature teratomas and eight non-Hodgkin B-cell lymphomas), clinical stage I. The intensity, the expression pattern and the percentage of neoplastic cell staining was recorded and correlated with the histologic type and vascular/lymphatic invasion. Dysadherin was not expressed in non-neoplastic germ cells, neither in CIS/ITGCNU, but it was highly expressed in all types of germ cell tumours, that demonstrated either embryonic phenotype or somatic differentiation, in most terminally differentiated neoplasms, and in all lymphomas. Dysadherin expression did not correlate with vascular invasion. Increased dysadherin expression was correlated with aberrant E-cadherin expression in most tumours. In 17% of embryonal carcinomas colocalisation of dysadherin and membranous E-cadherin staining was noted. This is the first report on dysadherin expression and its association with E-cadherin in testicular tumours. Since dysadherin is not normally expressed in non-neoplastic testis, it is conceivable that it plays a role in the neoplastic transformation of germ cells. In testicular tumours, as in other neoplasms, dysadherin downregulates E-cadherin expression, at least in part.

Cell cycle proteins in laryngeal cancer: role in proliferation and prognosis.

A study of laryngeal carcinomas was performed in order to analyze (a) the expression of p53/p21, cyclin D1/cyclin E, p21/p27 (b) the relation of normal and abnormal protein expression, with the proliferation status, as determined by the expression of Ki67 and PCNA and (c) the correlation of our findings with prognosis. We performed a retrospective analysis of 57 cases of squamous cell carcinomas of the larynx. We applied monoclonal antibodies against p53, p21, p27, cyclin D1, cyclin E, Ki67 and PCNA, using streptavidin-biotin method. Analysis of the p53/p21 proteins, revealed abnormalities in 25/37 cases (67.57%), while 12/37 (32.43%) cases displayed normal phenotype (p53-/p21-). Analysis of cyclins revealed overexpression in 17/48 cases (35.42), while the majority 31/48(64.58%) displayed normal phenotype (cyclin D1-/cyclin E-). Concerning CDKIs expression, the majority 30/50(60%) presented high levels of both inhibitors (p21+/p27+). Cases with simultaneous overexpression of CDKIs demonstrated significantly higher levels of Ki67 protein (p = 0.05). Analysis of p53/p21, cyclin D/cyclin E, p21/p27 patterns showed no association between the presence of one or two alterations and prognosis. In conclusion, we demonstrated that p53 tumor suppressor pathway is frequently disrupted in laryngeal cancer. Furthermore, levels of CDKIs, although they act as cell cycle activity blockers, are not reliable markers for the estimation of laryngeal neoplastic cells growth fraction.

Immunohistochemical study of angiogenesis and proliferative activity in epiretinal membranes.

Formation of epiretinal membranes (ERMs) is a serious complication of retinal diseases, the most important being proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). In this study, our goal was to (i) calculate the microvessel density (MVD), (ii) evaluate vascular endothelial growth factor (VEGF) expression and (iii) correlate angiogenesis with the proliferative activity as expressed by the expression of Ki67 marker, in both membrane types. We performed immunohistochemistry in 14 PVR and eight PDR membranes, using antibodies against CD34, VEGF, Ki67 and glial fibrillary acidic protein. PDR membranes presented higher average count of microvessels compared with PVR membranes (p = 0.0015). No differences were observed concerning VEGF expression (p = 0.1). The expression of Ki67 was not correlated with microvessel number or VEGF expression. Our study confirms the presence of vascularisation in PDR membranes, as well as the presence of VEGF even in avascular PVR membranes, suggesting that immunoreactivity for VEGF may not be accompanied by angiogenesis.

Dermatofibrosarcoma protuberans occuring in a child.

Dermatofibrosarcoma protuberans (DFSP) usually occurs in adults, however it can also occur in infancy and childhood. Diagnosis of DFSP in children is quite difficult given the rarity of the tumor and its variegated appearance. The behavior of this neoplasm is of borderline or intermediate malignancy with a high rate of recurrence but limited metastatic potential. We present the case of an eleven-year old boy who presented with a slightly raised, not tender lesion on his right shoulder. It had appeared two years before as a red-brown plaque and since then it had gradually grown to a nodule. An excisional biopsy was performed, and the diagnosis of DFSP was made based on the histological and immunohistochemical findings.

Giant simple renal cyst complicated with hypertension.

Solitary renal cysts are a common and usually asymptomatic occurrence in older patients. They may be associated with hypertension or abdominal disturbances, as they can be responsible for compression of surrounding tissues and distortion of renal vessels. This report presents an interesting case of a hypertensive patient with a solitary renal cyst of a marked size. Owing to the high risk of performing a surgical procedure in such a patient, a distinct therapeutic solution was opted for. Successful management of this case was achieved by a combination of percutaneous fluid aspiration and injection of alcohol and Vibramycin inside the cystic cavity. Percutaneous fluid evacuation combined with the administration of a sclerosing agent is suggested as a safe and effective alternative for cyst decompression and blood pressure normalisation.

Genetic models of human cancer as a multistep process. Paradigm models of colorectal cancer, breast cancer, and chronic myelogenous and acute lymphoblastic leukaemia.

Tumour formations arise as a consequence of alterations in the control of cell proliferation as well as with disorders in interactions between cells and their environment that result in invasion and metastasis. Recent advances in understanding the genetic basis of malignant diseases have been dominated by research in colorectal cancer. Genetic alterations of several proto-oncogenes and tumor-suppressor genes (e.g. APC/MCC, RAS, DCC, p53 mutations and/or allelic losses, hyperexpression of c-MYC and RB genes), as well as other genomic alterations, appear at characteristic stages of tumor development and are observed in most neoplasms. Generally, the normal cell has multiple independent mechanisms that regulate its growth and differentiation potential, and several separate events would, therefore, be needed to override these control mechanisms, as well as induce the other aspects of the transformed phenotype, like metastasis. These signals may be either positive or negative, and the acquisition of tumorigenicity results from genetic changes that affect these control points following a multistep mode. Statistics of the frequency of cancer incidence with age in humans indicate that for the genesis of e.g. lung carcinoma, five or six steps are required. Other types of cancers, such as leukemias and sarcomas, probably require quite a different number of rate-limiting changes. One of the best characterized tumours to provide a genetic model is colorectal tumorigenesis. Mutations implicated in breast cancer tumorigenicity are also studied and used as a genetic model in the literature worldwide. Finally, activation of c-abl in chronic myelogenous leukaemia (CML) and acute lymphoblastic leukaemia could also be presented as an example, which provides probably the strongest evidence for the role of proto-oncogenes in human malignancy process.

Expression patterns of cyclins D1, E in laryngeal epithelial lesions: correlation with other cell cycle regulators (p53, pRb, Ki-67 and PCNA) and clinicopathological features.

The expression of cell-cycle progression molecules cyclin D1 and cyclin E were immunohistochemically examined in a series of 64 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 34 cases of dysplasia, 11 papillomas and 23 cases of keratosis. The results of their expression were compared with two cell-cycle implicated tumor suppressor proteins p53 and pRb as well as with two proliferation associated indices PCNA and Ki-67 in an attempt to elucidate their potential role in the pathogenesis and progression of these lesions. Nuclear staining for cyclin D1 and E (>5% positive cells) was observed in 19% and 39.7% of the laryngeal carcinomas, respectively. Significantly elevated levels of cyclin D1 and E in invasive laryngeal carcinomas compared with in situ carcinomas were revealed (p=0.045 and p=0.0003, respectively). High levels of cyclin D1 and E expression were correlated with increased Ki-67 score (p=0.037 and 0.017 respectively). A significant positive correlation between cyclin D1 and E was also detected in carcinomas (p=0.018). Decreased levels of cyclins D1 and E in the group of in situ carcinomas compared with those of dysplastic cases and papillomas were also observed. In the dysplastic lesions cyclin D1 expression was correlated with pRb expression (p=0.02). In the cases of keratosis cyclins D1 and E expression were correlated with pRb (p=0.002 and p=0.036, respectively), while cyclin D1 was associated with PCNA (p=0.008) and Ki-67 score (p=0.009). The prognostic significance of cyclins D1, E in determining the risk of recurrence and overall survival with both univariate (long-rang test) and multivariate (Cox regression) methods of analysis showed no statistically significant differences. We conclude that the expression of cyclins D1 and E in squamous cell carcinomas of the larynx does not seem to have a prognostic significance. In addition, their expression may be involved in the development of laryngeal lesions, implicated in cell proliferation, with other cell cycle related proteins, probably by different molecular pathways.

Expression of cyclin-dependent kinases inhibitors p21(WAF1) and p27(KIP1) in benign, premalignant and malignant laryngeal lesions. correlation with cell cycle regulatory proteins.

BACKGROUND: Cell cycle progression and transition of cells from the first gap phase (G1) to the DNA replication phase (S) depend on a finely tuned balance between the levels of cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDKIs). MATERIALS AND METHODS: We analyzed 57 squamous cell invasive carcinomas of the larynx, 10 in situ carcinomas, 56 cases of dysplasia, 11 papillomas and 26 keratosis. We investigated: a) the immunohistochemical expression of CDKIs, p21 and p27, b) any possible relation between normal and abnormal immunoprofiles of these proteins and p53 protein and proliferation status as determined by the expression of Ki67 and PCNA, and c) their presence in pre-malignant and malignant laryngeal lesions. RESULTS: Expression of p21 and p27 was observed in 58.9% and 89.5% of the laryngeal carcinomas, respectively. High levels of p21 were significantly correlated with increased cyclin D (p=0.001), cyclin E (p<0.001) and Ki67 (p<0.001), while increased expression levels of p27 were associated with p53 accumulation (p=0.02) and with increased proliferation status as expressed by Ki67 (p=0.05). CONCLUSION: Due to the increased expression levels of CDKIs in laryngeal carcinomas, we suggest the existence of a mechanism by which tumor cells tolerate the inhibitory effect of these proteins on cell cycle progression.

The role of ascorbic acid, selenium, and glutathione on benzo[a]pyrene-induced carcinogenesis in wistar rats.

PURPOSE: The carcinogenic action of polycyclic aromatic hydrocarbons (PAHs) can be inhibited by endogenous or exogenous compounds. This study was designed to elucidate the modifying action of 3 endogenous inhibitors- ascorbic acid (vit C) used alone, and selenium (Se) used in combination with glutathione (GSH). MATERIALS AND METHODS: Chemical carcinogenesis was induced by benzo[a]pyrene(BaP). A hundred wistar rats were divided into 3 groups: the first group (G I) consisted of 42 animals, representing the control group. The two experimental groups (G II and G III) consisted of 38 and 20 rats, respectively. All groups were injected with BaP(10.08 mg subcutaneously-s.c). The first experimental G II was given only vit C (520 mg in 2% sugar solution per os - p.o.). The second experimental G III was given Se (0.1 mg p.o.) with GSH (200 mg p.o.). Tumor incidence and mean survival time were determined. Histological examination of the developed and excised tumors took place following death. The carcinogenic potency (CP) and anticarcinogenic potency (AP) of the substances used were calculated. RESULTS: A statistically significant difference regarding the mean survival time in the two experimental groups (238.4-/+31 days and 344.9-/+48 days, respectively) compared to the control group (183.8-/+28 days) was found (p < 0.001). The CP of each of the 3 groups was 54.3, 41.2, and 28.9 units, respectively. The AP of vit C used alone was 13.1 units, representing a significant anticarcinogenic effect. The combination of Se + GSH showed an AP of 25.4 units, resulting in a significant prolongation of the mean survival time, which is considered a potent anticarcinogenic effect. Furthermore, a statistically significant difference was found also when the mean survival time of G III animals was compared with G II. CONCLUSION: Vit C on its own and Se in combination with GSH represent strong endogenous inhibitors that can inhibit/reduce the carcinogenic action of BaP-induced carcinogenesis in wistar rats. The combination therapy used offered better in vivo results.