EBV-Associated Gastric Cancer; An In Situ Hybridization Assay on Tissue Microarray: A Multi-Region Study from Four Major Provinces of Iran.

BACKGROUND: Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran. METHODS: Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics. RESULTS: Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075). CONCLUSION: EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.

Sentinel Node Biopsy in Early Breast Cancer Patients with Palpable Axillary Node.

BACKGROUND: Sentinel lymph node biopsy is a reliable method for evaluation of the axillary lymph node status in early stage breast cancer patients with non-palpable lymph nodes. The present study evaluated the status of sentinel and non-sentinel lymph nodes in T1T2 patients with palpable axillary lymph nodes. MATERIALS AND METHODS: One hundred and two women with early breast cancer were investigated in this study. Patients were selected for axillary sentinel lymph node biopsy and then surgery .Then the rates of false negative and true positive, and diagnostic accuracy of sentinel lymph nodes biopsy were evaluated. In addition, the hormone receptors status of the tumor was determined through IHC and data was analyzed in SPSS21. RESULTS: In this study, the mean age of the patients was 49 years, 85% had invasive ductal carcinoma  in their pathology reports, 77% were ER/PR positive, 30% HER2 positive and 9.8% triple negative and 69% had KI67<14%. In frozen pathology, 15.7 and 84.3% were sentinel positive and negative, respectively, and in the final pathology, 41 and 58.8% were sentinel positive and negative, respectively. This difference arises from the false negative rate of the frozen pathology, which was about 31.3%. The sensitivity, specificity, and diagnostic accuracy of the frozen section were 24, 90 and 43%, respectively. Lymphovascular invasion is an important effective factor in the involvement of sentinel and non-sentinel lymph nodes. Statistical analysis showed that the probability of sentinel and non-sentinel lymph nodes involvement was higher in receptor positive patients and those with KI67>14% (p<0.002) whereas the rate of involvement was lower in triple negative patients. CONCLUSION: Sentinel node biopsy can be used in a significant percentage of breast cancer patients with palpable and reactive axillary lymph nodes.

Is Necessary Intraoprative Frozen Section In Sentinel Lymph Node Biopsy For Breast Cancer Patients?

BACKGROUND: Improvements in the process of staging and surgical treatment of axillary lymph nodes in recent years, have led to the use of intra operative frozen section pathology to examine the sentinel lymph node biopsy in breast cancer patients. MATERIALS AND METHODS: we evaluated the results of the Sentinel biopsy in 102 patients with early stage breast cancer, which were negative clinical lymph nodes, and analyzing the true positive and false negative rate, diagnostic accuracy of frozen section lymph node biopsy. It also studied the factors affecting the sentinel and non-sentinel lymph nodes in patients treated by axillary lymph dissection. RESULTS: In this study, we investigated 102 patients' stage 1and 2 breast cancer with clinical negative axillary lymph node and candidates for sentinel lymph node biopsy, were placed under investigation. 15.7 % of the real positive results of sentinel and 62.7 % of the real negative and 2 % false positives and 20.9 % false negative results and% 78. 4 diagnostic accuracy, has been frozen section. Among the patients who were initially or delayed in the axillary dissection, 37% had more than two lymph nodes. While in general, 16.7% of patients had a need for axillary lymph node dissection based on z11 criteria. Lymph-vascular invasion was a major contributor to lentil involvement in Sentinel and non-Sentinel nodes. CONCLUSION: Frozen section pathology during the operation of sentinel lymph node biopsy has been initiated to prevent the need for a reoperation in early stage breast cancer patients. However, due to low tumor burden in patients who are candidates for this procedure, and the constraints in the initial sections and their false negative results, also the removal of frozen section will not have an effect on the rate of increasing reoperation and can be effective in reducing the time and cost of surgery.

Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice.

OBJECTIVE: To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. METHODS: Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. CONCLUSIONS: The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.

Effects of some natural products from fungal and herbal sources on Giardia lamblia in vivo.

Giardia lamblia (G. lamblia) is the most widely known protozoan parasite that causes human gastrointestinal infection worldwide. Some natural compounds exhibited pivotal effects against different infectious diseases. In this research, the antigiardial activity and cytotoxicity of fungal chitosan, nano-chitosan, Rhamnus cathartica (R. cathartica) and emodin were evaluated in Balb/c mice. Genotyping of G. lamblia was assessed by PCR-RFLP technique. Different concentrations of mentioned compounds were used to check their antigiardial and cytotoxicity effects on human intestinal epithelial cells (HT-29) after 24, 48 and 72 h. The G. lamblia strain used in the current work was genotyped and revealed as an AII assemblage. All the concentration showed acceptable activity against G. lamblia cysts and trophozoites in comparison to the negative and positive controls (furazolidone and metronidazole) in vitro (P 0.05). The maximum mortality rate (100%) was achieved at 100 and 50 µg kg-1 concentrations after 48 and 72 h of exposure time, respectively. Our results provide significant information about the new antigiardial agent and proposed the nano-chitosan and emodin for the development of new drugs against G. lamblia in the future.

Immunohistochemical Expression of Nanog and Its Relation with Clinicopathologic Characteristics in Breast Ductal Carcinoma

Background: Cancer stem cells (CSCs) are a group of tumor cells with self-renewal property and differentiation potential. CSCs play a crucial role in malignant progression of several types of tumors. However, what is still controversial is the clinicopathological relationship between the Nanog marker and its prognostic value in the patients with breast cancer. The expression of Nanog in the patients with breast cancer and its correlation with clinicopathological prognostic factors was explored in the present study. Methods: A sample of 120 breast cancer tissues was obtained from the patients who referred to Imam Khomeini Hospital in Sari City, Iran during January 2012 and December 2016. The associations between Nanog expression and clinicopathological factors were analyzed based on immunohistochemical analysis. Results: The expression of Nanog was detected in 67 (55.8%) patients with a high expression rate in 24 (36%) cases (staining index ≥3). Moreover, there was a statistically significant relationship between Nanog expression and clinicopathological factors, including tumor grade (p = 0.001), lymph node metastasis (p = 0.01), and the stage of the disease (p = 0.003). Conclusion: Findings of the study indicate that Nanog may act as a biomarker for prognostic prediction in patients with breast cancer.

Detection of human papillomavirus DNA in gastric carcinoma specimens in a high-risk region of Iran.

Gastric cancer is the fourth most common type of cancer worldwide and is associated with high mortality rates. The incidence of gastric cancer varies widely in different geographical regions. For example, in Iran, the most northern and northwestern regions are considered to be high-risk areas for gastric cancer. The aim of the present study was to determine the distribution of human papillomavirus (HPV) genotypes among patients with gastric carcinoma in Mazandaran province, Northern Iran, which is a high-risk area. A total of 100 paraffin-embedded tissue samples were obtained from 70 males and 30 females with gastric carcinoma, diagnosed between 2006 and 2013, in the Imam Khomeini Hospital (Sari, Iran). GP5+/GP6+ general primers were applied for detection of HPV DNA in the specimens. Positive samples were then selected and high-risk HPV genotyping was performed. The samples were analyzed by polymerase chain reaction and five (5%) samples were identified to be positive for HPV DNA [four male (5.7%) and one female (3.3%)]. Three (60%) samples were positive for HPV-16, one (20%) sample was positive for HPV-18 and one (20%) sample was positive for HPV-45. Following pathological diagnosis, 88 samples were identified as gastric adenocarcinoma, nine samples were gastric lymphoma, and three samples were gastric and esophagus adenocarcinoma. According to the findings of the present study and the rate of HPV infection in patients with gastric carcinoma, an association between HPV infection and gastric carcinoma in subjects from Northern Iran was not identified.

Cancer stem cells CD133 and CD24 in colorectal cancers in Northern Iran.

AIM: We aimed to study the expression of CD24 and CD133 in colorectal cancer and normal adjacent tissues to assess a relationship between these markers and clinic-pathological characteristics and patient's survival. BACKGROUND: Cancer stem cells are a group of tumor cells that have regeneration and multi-order differentiation capabilities. PATIENTS AND METHODS: Expression of CD24 and CD133 was studied in a paraffin block of colorectal cancer and normal tissues near tumors with the immuneohistochemical method in patients who were referred to Imam Khomeini Hospital in Sari. RESULTS: A total of 50 samples (25 males and 25 females) with a mean age of 67.57±13.9 years old with range 28-93 years, included 3 mucinous carcinoma and 47 adenocarcinoma. Expression of CD133 marker was negative in 29 cases and positive in 21 cases. Expression of CD24 in tissue near tumor cells was found in 30% of available samples. The relationship between expressing CD24 with treatment (surgery and chemotherapy) was significant and its relationship with patient's survival was insignificant statistically. However, there was a clear difference as mean survival age of patients based on CD24 expression was 26.64±18.15 for negative cases and 41.75±28.76 months for positive cases. CD24 and CD133 expressions and their co-expression with other clinic-pathological factors were not significant. CONCLUSION: During this study, the relationship between CD24 and treatment type was significant. To confirm this result, various studies with high sample numbers and other stem cell markers are recommended.

Primary Cardiac Angiosarcoma in a Middle Aged Woman.

INTRODUCTION: Primary cardiac angiosarcoma is the most common primary sarcoma in adults between the 3rd and 4th decades of life. Nearly 90% of angiosarcomas occur in the right atrium, which is responsible for the late onset of symptoms. CASE PRESENTATION: We presented a 56-year-old woman admitted to our center with lung emboli symptoms. Transthoracic and transesophageal echocardiography (TTE and TEE) demonstrated very large size (more than 10 cm diameter) multilobulated mass with mobile particles extended from the right atrium to the right ventricle and the right ventricular outflow tract which destructed the right atrium (RA) wall and penetrated to the pericardial space. CONCLUSIONS: Unfortunately the tumor was unresectable and just an incisional biopsy was performed. She received chemotherapy as palliative care.

Relationship of cortisol, norepinephrine, and epinephrine levels with war-induced posttraumatic stress disorder in fathers and their offspring.

OBJECTIVE: To compare afternoon serum/plasma levels of hormones in four groups: (A) veterans with posttraumatic stress disorder (PTSD), (B) offspring of PTSD veterans, (C) veterans without PTSD, and (D) offspring of non-PTSD veterans. METHODS: Evaluation consisted of a semi-structured interview for axis I and II diagnoses, followed by measurement of afternoon serum cortisol and plasma epinephrine and norepinephrine by ELISA (Diametra) and LND (LDN Labor Diagnostika Nord GmbH & Co. KG) respectively. Data were analyzed using descriptive statistics and the Student t, Kolmogorov-Smirnov, and nonparametric Mann-Whitney tests. RESULTS: One hundred and sixty-eight volunteers were investigated across the four groups. The groups were similar in terms of demographic characteristics, war experience and traumatization, and psychiatric and medical conditions other than PTSD (group A was similar to group C and group B was similar to group D). Between-groups comparisons did not yield statistically significant differences. Post-hoc analyses revealed significant differences in afternoon cortisol level between the offspring of veterans with current/past history of PTSD and the offspring of veterans without a history of PTSD. CONCLUSION: We only found decreased cortisol levels in offspring of veterans after rearranging the groups to reflect previous history of PTSD. Further studies are required to investigate the relationship between cortisol levels and the transgenerational effects of trauma and parental PTSD.

Relationship of cortisol, norepinephrine, and epinephrine levels with war-induced posttraumatic stress disorder in fathers and their offspring

Objective: To compare afternoon serum/plasma levels of hormones in four groups: (A) veterans with posttraumatic stress disorder (PTSD), (B) offspring of PTSD veterans, (C) veterans without PTSD, and (D) offspring of non-PTSD veterans. Methods: Evaluation consisted of a semi-structured interview for axis I and II diagnoses, followed by measurement of afternoon serum cortisol and plasma epinephrine and norepinephrine by ELISA (Diametra) and LND (LDN Labor Diagnostika Nord GmbH & Co. KG) respectively. Data were analyzed using descriptive statistics and the Student t, Kolmogorov-Smirnov, and nonparametric Mann-Whitney tests. Results: One hundred and sixty-eight volunteers were investigated across the four groups. The groups were similar in terms of demographic characteristics, war experience and traumatization, and psychiatric and medical conditions other than PTSD (group A was similar to group C and group B was similar to group D). Between-groups comparisons did not yield statistically significant differences. Post-hoc analyses revealed significant differences in afternoon cortisol level between the offspring of veterans with current/past history of PTSD and the offspring of veterans without a history of PTSD. Conclusion: We only found decreased cortisol levels in offspring of veterans after rearranging the groups to reflect previous history of PTSD. Further studies are required to investigate the relationship between cortisol levels and the transgenerational effects of trauma and parental PTSD. .

The prognostic impact of EGFR, ErbB2 and MET gene amplification in human gastric carcinomas as measured by quantitative Real-Time PCR.

PURPOSE: Identification of critical genes which play pivotal roles in controlling tumor growth and survival will establish the basis for developing therapeutic targets. In this study, we focused on frequencies of EGFR, ErbB2 and MET gene amplification in gastric cancer patients to develop personalized medicine to improve the treatment. METHOD: EGFR, ErbB2 and MET gene amplification, and mRNA expression were analyzed by the quantitative Real-Time PCR in paraffin-embedded samples from 115 patients with gastric cancer. RESULTS: EGFR, ErbB2 and MET genes were amplified in 11.3 % (13/115), 6.1 % (7/115) and 19.1 % (22/115) of cancerous specimens, respectively. The correlation coefficient test clearly indicated that gene amplification in these three genes was positively correlated with mRNA transcription (EGFR: R = 0.631, p = 0.009; ErbB2: R = 0.652, p = 0.023; MET: R = 0.715, p < 0.001). EGFR and MET gene amplification was significantly associated with Ki-67 MI (p = 0.022 and p = 0.015). MET amplification was also significantly associated with age of ≥60 years (p = 0.021) and tumor size of ≥5 cm (p = 0.032). MET amplification, but not EGFR and ErbB2, was a significant prognostic factor in poor survival among patients with gastric cancer. CONCLUSIONS: EGFR, ErbB2 and MET genes are frequently amplified in gastric carcinoma. EGFR, ErbB2 and MET gene amplification is positively correlated with mRNA transcription. MET gene amplification correlates with a poor prognosis and poor survival in gastric carcinomas.

Protective effects of thymol against nephrotoxicity induced by cisplatin with using 99mTc-DMSA in mice.

BACKGROUND: In this study, we investigated the protective effect of thymol as a natural compound against cisplatin-induced nephrotoxicity by quantitative renal 99mTc-DMSA uptake and compared its effect with histopathology in mice. MATERIALS AND METHODS: Mice were divided into six groups as control, cisplatin (7.5 mg/kg, intraperitoneally), thymol+cisplatin (thymol; 50 and 150 mg/kg+cisplatin; 7.5 mg/kg) and thymol (50 and 150 mg/kg). Thymol was orally administrated for two days before cisplatin injection and continued for 4 days. (99m)Tc-DMSA was injected through the tail of mice after the drug administration. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. In other experiment, kidneys of treated mice were assessed for histopathology. RESULTS: 99mTc-DMSA uptake per gram tissue of the kidneys as %ID/g was 85.27±21.81, 45.55±5.50, 65.02±32.21 and 88.46±20.46 in the control, cisplatin, thymol (50 mg/kg)+cisplatin and thymol (150 mg/kg)+cisplatin. Thymol administration with cisplatin resulted in a significant increase in the level of %ID/g. Histopathological examinations showed a protective effect of thymol against cisplatin nephrotoxicity in mice. CONCLUSION: The results showed that thymol significantly attenuates the cisplatin-induced nephrotoxicity in mice, and 99mTc-DMSA uptake in kidney is a suitable method for assessment of nephrotoxicity in mice.

Genoprotective effects of Origanum vulgare ethanolic extract against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.

CONTEXT: Cyclophosphamide (CP), an alkylating chemotherapeutic agent, can bind DNA, causing chromosome breaks, micronucleus (Mn) formation, and cell death. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against DNA damage. OBJECTIVE: The genoprotective effect of O. vulgare ethanolic extract against CP-induced genotoxicity in mouse bone marrow cells was evaluated using a Mn assay. MATERIALS AND METHODS: Mice were pre-treated with aerial parts of O. vulgare ethanolic extract at different doses (50, 100, 200, or 400 mg/kg) for 7 d. One hour after the last administration of O. vulgare, animals were injected with CP at 200 mg/kg. After 24 h, the bone marrow cells of both femurs were flushed and the frequency of MnPCEs was evaluated to measure the chromosomal damages. In addition, the number of PCEs per 1000 NCEs in each animal was recorded to evaluate the bone-marrow suppression; mitotic activity was calculated as [PCE/(PCE + NCE)] × 100 to assess the cell division. RESULTS: At 400 mg/kg, O. vulgare displayed its maximum protective effect, reduced the number of MnPCEs from 10.52 ± 1.07 for CP group to 2.17 ± 0.26 and completely normalized the mitotic activity (p < 0.001). Origanum vulgare also led to significant proliferation and hypercellularity of immature myeloid elements after the mice were treated with CP, mitigating the bone marrow suppression. DISCUSSION AND CONCLUSION: Origanum vulgare ethanolic extract exerts a potent genoprotective effect against CP-induced genotoxicity in mice bone marrow, which might be possibly due to the scavenging of free radicals during oxidative stress conditions.

Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice.

UNLABELLED: Abstract Context: Despite its wide clinical use, cyclophosphamide (CP), an alkylating chemotherapeutic agent, possesses many adverse effects, including hepatotoxicity. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against above-mentioned damage. OBJECTIVE: This study evaluated the protective effects of O. vulgare extract on CP-induced liver toxicity. MATERIALS AND METHODS: Mice were pretreated with aerial parts of O. vulgare ethanolic extract (intraperitoneally) at doses of 50, 100, 200, and 400 mg/kg for 7 consecutive days before the administration of a single 200 mg/kg intraperitoneal dose of CP 1 h after the last injection of O. vulgare. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination. RESULTS: Serum levels of hepatic markers were increased after CP treatment but restored in the O. vulgare-pretreated groups. The serum ALT, AST, and ALP of the CP group were 196.49 ± 3.82, 143.78 ± 4.79, and 203.18 ± 3.81 IU/l, respectively. However, pretreatment with 400 mg/kg O. vulgare significantly decreased the serum ALT, AST, and ALP to 52.49 ± 2.18, 44.78 ± 2.06, and 65.62 ± 1.73 IU/l, respectively (p < 0.001). Histological examinations also confirmed the protective effects of O. vulgare against CP-induced liver toxicity. DISCUSSION AND CONCLUSION: Our results reveal that O. vulgare with high amount of flavonoids and phenolic compounds induces potent hepatoprotective mechanisms against CP. Therefore, O. vulgare might help defend the body against the side effects, particularly hepatic damages induced by chemotherapeutic agents.

Prophylactic efficacy of melatonin on cyclophosphamide-induced liver toxicity in mice.

The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide (CP) in mice. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mg/kg CP. 24 hr after CP administration, the mice were anesthetized, blood was then removed, and serum toxicity enzymes activities were evaluated. After the blood sampling, all animals were killed, livers were then removed, and histological studies were conducted. Serum toxicity marker enzymes were significantly increased after CP treatment but restored in melatonin pretreated groups. In addition, administration of CP induced necrotic hepatocyte with small crushed nuclei, portal space with severe inflammation, and hepatocytes surrounded by lymphocytic infiltration in hepatic tissues. However, melatonin effectively protected against CP-induced histopathological abnormalities in the liver tissues. Our results reveal that melatonin produces a potent hepatoprotective mechanism against CP. Therefore, melatonin could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.

Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

Nephroprotective effects of Feijoa Sellowiana leaves extract on renal injury induced by acute dose of ecstasy (MDMA) in mice.

OBJECTIVE(S): Because of the high total phenolic contents of Feijoa sellowiana, its nephroprotective effect was determined in 3,4-methylene dioxymethamphetamine (MDMA) treated mice. MATERIALS AND METHODS: Animals received 10, 20 and 40 mg/kg doses of aqueous or methanol extract of F. sellowiana leaves, intra-peritoneally. After one hour, an acute administration of MDMA (20 mg/kg, IP) was injected. Nephroprotective effect was assayed by determination of serum creatinine, serum urea and kidney glutathione level. Histopathological study was also used. Results : Both extracts at 40 mg/kg resulted in a significant reversal in the raised serum creatinine levels (P <0.05). Not statistically significant was observed in effect of two extracts (P>0.05). A decrease in urea/ creatinine ratio was observed following aqueous extract treatment. Methanolic extract showed higher activity in increasing kidney glutathione (P<0.001 compared to MDMA group). Methanol extract showed higher protective activity in histopathology study. CONCLUSION: F. sellowiana extract resulted in a markedly decrease in the nephrotoxicity of MDMA in mice.

An ethanol extract of Origanum vulgare attenuates cyclophosphamide-induced pulmonary injury and oxidative lung damage in mice.

CONTEXT: Injury to normal tissues is the major limiting side effect of using cyclophosphamide (CP), an antineoplastic alkylating compound. OBJECTIVE: This study was undertaken to evaluate the protective effect of an extract of Origanum vulgare L. (Lamiaceae), an antioxidative medicinal plant, against CP-induced oxidative lung damage in mice. MATERIALS AND METHODS: Mice were pre-treated with various doses of O. vulgare extract (50, 100, 200, and 400 mg/kg) for 7 consecutive days followed by an injection with CP (200 mg/kg b.w.) One hour after the injection of O. vulgare on the last day, mice were injected with CP; 24 h later, they were euthanized, their lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with O. vulgare significantly reduced the levels of lipid peroxidation and attenuated the alterations in glutathione content and superoxide dismutase activity induced by CP in lung tissue. In addition, O. vulgare effectively alleviated CP-induced histopathological changes in lung tissue. CONCLUSIONS: Our results revealed that O. vulgare protects lung tissues from CP-induced pulmonary damage and suggest a role for oxidative stress in the pathogenesis of lung disease produced by CP. Because O. vulgare has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a supplement for reducing lung damage in patients undergoing chemotherapy.

Cancer Stem Cell Markers CD44, CD133 in Primary Gastric Adenocarcinoma.

Cancer stem cells (CSCs) are unique subpopulations that have the capacity to drive malignant progression with renewal abilities. Recently the role of some of CSCs in gastric adenocarcinoma has been studied. This study was performed in order to evaluate CD44 and CD133 expressions by immunohistochemistry in 95 primary gastric adenocarcinoma and their relation to clinical and pathological parameters of these tumors. There was a significant correlation between CD44 expression and cancer subtype (intestinal), tumor size (4-8 cm), depth of invasion, no lymphatic/vascular invasion and moderate differentiation. There was a significant correlation between CD133 expression and patient's age (> 65 years), cancer subtype (intestinal), tumor size (4-8 cm), depth of invasion and moderate differentiation. CSC markers like CD 44 and CD133 had high expression in primary gastric adenocarcinoma and had some relations to clinical and pathological parameters of tumors.