Molecular Imaging of HER2 Expression in Breast Cancer patients Using the [99mTc] Tc-Labeled Small Peptide.

PURPOSE: The accurate determination of human epidermal growth factor receptor 2 (HER2) status can predict response to treatment with HER2-targeted therapy for HER2-positive breast cancer patients. [99mTc]Tc-HYNIC-(Ser)3-LTVPWY ([99mTc]Tc-HYNIC-LY) is a small synthetic peptide molecule targeting of the HER2 receptor. This clinical study evaluated the pharmacokinetic, dosimetry, and efficacy of [99mTc]Tc-HYNIC-LY for determining the HER2 status in primary breast cancer patients. MATERIALS AND METHODS: In total, 24 women with suspected primary breast cancer received an intravenous injection of approximately 20 µg (∼740 MBq) of [99mTc]Tc-HYNIC-LY. In the first 3 patients, blood levels of radioactivity were analyzed for pharmacokinetic evaluation and planar gamma camera imaging was conducted at 30 min and 1, 2, 4, and 24 hour after injection for dosimetry assessment. In the last 21 patients, planar imaging was performed at the baseline, as well as 1, 2, 3, and 4 hour, followed by single-photon emission computed tomography (SPECT) imaging after 4 hour to evaluate the tumor-targeting potential in primary lesions. RESULTS: Injection of [99mTc]Tc-HYNIC-LY was safe and well tolerated. Fast blood clearance provided high-contrast HER2 imaging within 1 to 4 hour. The highest absorbed radiation dose was found for kidneys (6.78E-03 ± 2.62E-04 mSv/MBq), followed by the heart (3.73E-03 ± 1.98E-04 mSv/MBq). The [99mTc]Tc-HYNIC-LY peptide was able to detect HER2 status in primary tumors at an acceptable level. CONCLUSION: The findings of this study indicated that [99mTc]Tc-HYNIC-LY SPECT is safe and feasible for the identification of HER2-positive lesions in primary breast cancer patients, and may provide an accurate and non-invasive modality for guiding HER2 targeted therapy.

Evaluation of Antiphospholipid Antibodies in COVID-19 Patients with Coagulopathy.

Background: Due to the importance of recent published studies regarding the thrombotic events in COVID-19 patients, the purpose of this study was to evaluate the frequency of antiphospholipid antibodies in COVID-19 patients with coagulopathy. Materials and Methods: The present cross-sectional study was conducted on COVID-19 patients with coagulopathy admitted to Imam Khomeini Hospital in Sari, Iran, between June and September in 2020. Later on, the levels of anti-phospholipid antibodies (aPL-ab) and biochemical factors were measured. Results: This study was performed on 40 patients. Individuals who were positive for at least one of the aPL-ab were classified in the group of aPL-ab positive; according to which 29 patients (72.5%) had no positive aPL-ab and 11 patients (27.5%) had at least one positive aPL-ab. 8 patients were only positive for lupus anticoagulant (LA) assay, one patient had B2GPI- IgM, one patient had aCL-IgG and only one patient had two positive simultaneous tests for LA and aCL-IgG. Thrombotic events have been found in 7 patients (17.5%) of which, three patients with deep vein thrombosis, one patient with pulmonary embolism, two patients with stroke, and one patient with myocardial infarction. The values of aPTT for the screening of Lupus anticoagulant assay were significantly different between the two groups, although there was no significant difference between the two groups in the co-morbidities, disease severity, death and laboratory tests (P> 0.05). Conclusion: Despite the high incidence of thrombotic complications reported in COVID-19 patients in the current study, the levels of antiphospholipid antibodies had no significant correlation with the occurrence of thromboembolic events and disease outcome in COVID-19 patients with coagulopathy.

Interdigitating Dendritic Cell Tumor of Submandibular Lymph Node: Case Report and Literature Review.

Dendritic cells (DCs) are key arms of immune system, which act in antigen presenting processes, and are considered as a bridge between innate and adaptive immune responses. DCs are found in both lymphoid and non-lymphoid organs. They are called interdigitating dendritic cells (IDCs) in secondary lymphoid organs. IDCs lack lineage surface markers and are positive for S-100 and vimentin. IDC sarcoma (IDCS) is a very rare neoplasm, which mainly affects lymph nodes, though there are reports of extra-nodal involvement. IDCS is thought to have poor prognosis. Although there is no consensus on the treatment modalities, such options as radical surgery, chemotherapy, and radiotherapy are performed depending on severity and site of the lesion. In this study, we present a case of IDCS in a 53-year-old male with a history of several skin lesions and prior diagnoses of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and metatypical carcinoma (MTC).

Invasion of poorly differentiated large-cell neuroendocrine tumor of the lung through right pulmonary veins into the left atrium: A very rare case report.

Intracavitary cardiac metastasis is a rare manifestation of primary lung cancer which can be associated with a very poor prognosis. In this condition, the right chambers of the heart are more commonly involved and the invasion of the left atrium (LA) through the venous routes is highly exceptional. Poorly differentiated large-cell neuroendocrine tumors also include only 3% of all primary lung carcinomas which can have adverse outcomes. Therefore, in this report, a rare case of a 72-year-old male patient with poorly differentiated large-cell neuroendocrine carcinoma of the right lung spreading to the LA through the right pulmonary veins was described.

Evaluation of adverse effects of chemotherapy regimens of 5-fluoropyrimidines derivatives and their association with DPYD polymorphisms in colorectal cancer patients.

BACKGROUND: 5-Fluorouracil (5-FU) and capecitabine are fluoropyrimidine derivatives that mainly metabolized with dihydropyrimidine dehydrogenase enzyme (DPD). The genetic polymorphism in the genes encoding this enzyme may result in a decrease or loss of enzyme activity which may lead to the accumulation of medicines, their metabolites and potential toxicity. METHOD: This cross-sectional study was conducted on 88 participants with colorectal cancer (CRC). After DNA extraction, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the DPD gene (DPYD) polymorphisms including IVS 14 + 1 G > A, 2846 A > T and 2194 G > A. Chemotherapy-induced side effects were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE Version 5.0). RESULT: Data were collected from 227 chemotherapy cycles of 88 patients with CRC. In a comparison of FOLFOX and FOLFIRI regimens, there was no significant difference in the occurrence of chemotherapy-induced diarrhea, nausea, vomiting and oral mucositis. However, the peripheral neuropathy was more frequent in patients who were treated with FOLFOX (P <  0.001) and hair loss was more common in patients who received FOLFIRI regimen (P = 0.048). Incidence of the DPD IVS14 + 1 G > A polymorphism was observed in four patients (5.5%). There was no association between IVS14 + 1 G > A polymorphism and the occurrence of adverse reactions. CONCLUSION: FOLFOX and FOLFIRI were the most common regimens in CRC patients and their toxicity profile was different in some adverse reactions. Prevalence of IVS14 + 1G > A variant was relatively higher than other similar studies. TRIAL REGISTRATION: Approval code; IR.MAZUMS.REC.95.2480.

Epigenetic alterations of CYLD promoter modulate its expression in gastric adenocarcinoma: A footprint of infections.

Gastric cancer (GC) is one of the most common causes of cancer-related death in the world, with multiple genetic and epigenetic alterations involved in disease development. CYLD tumor suppressor gene encodes a multifunctional deubiquitinase which negatively regulates various signaling pathways. Deregulation of this gene has been found in different types of cancer. This study aimed to evaluate for the first time the CpG island methylation pattern of CYLD gene promoter, and its expression level in gastric adenocarcinoma. CYLD messenger RNA expression and promoter methylation in 53 tumoral and their non-neoplastic counterpart tissues were assessed using quantitative polymerase chain reaction and bisulfite sequencing. Also, we investigated the impacts of the infectious agents including Helicobacter pylori (H. pylori), EBV, and CMV on CYLD expression and promoter methylation in GC. Results showed that the expression level of CYLD was downregulated in GC, and was significantly associated with gender (female), patient's age (<60), high grade, and no lymph-node metastasis (p = 0.001, 0.002, 0.03, and 0.003, respectively). Among the 31 analyzed CpG sites located in about 600 bp region within the promoter, two CpG sites were hypermethylated in GC tissues. We also found a significant inverse association between DNA promoter methylation and CYLD expression (p = 0.02). Furthermore, a direct association between H. pylori, EBV, and CMV infections with hypermethylation and reduced CYLD expression was observed (p = 0.04, 0.03, and 0.03, respectively). Our findings indicate that CYLD is downregulated in GC. Infectious agents may influence CYLD expression.

MYC, BCL2, and BCL6 rearrangements in primary central nervous system lymphoma of large B cell type.

Primary central nervous system lymphoma (PCNSL) is a rare specific subtype of non-Hodgkin lymphoma limited to the brain, leptomeninges, spinal cord, or eyes without any systemic presentation and relapse which mostly takes place in CNS. In more than 95% of patients, it is of diffuse large B cell lymphoma (DLBCL) type. Categorizing PCNSL to germinal center cell like or activated B cell like, as we usually do for DLBCL NOS, may not be applicable for predicting outcome. Possible prognostic significance of MYC, BCL2, and/or BCL6 rearrangements may be important given what we know about their impact in systemic DLBCL, but we have limited knowledge about the status of double or triple hit molecular changes in PCNSL. Here, we have investigated prevalence of these molecular alterations in PCNSL. Two independent tissue microarrays constructed from 78 formalin-fixed paraffin-embedded blocks of confirmed PCNSL were tested for rearrangement of MYC, BCL2, and BCL6 by interphase fluorescent in situ hybridization (FISH) using break apart dual color probes. BCL6 translocation was detected in 15 (12%) cases. Translocation involving MYC and BCL2 was identified in 3 cases (3.8%) and 1 case (1.3%) respectively. One double hit lymphoma was discovered with both MYC/BCL2 translocation (1.3%). To the best of our knowledge, few organized studies have been conducted for MYC, BCL2, and/or BCL6 rearrangement in PCNSL. This study is evaluating large number of PCNSL. Double or triple hit events which are rarely seen in PCNSL.

Ovarian Cancer or Hydatidosis? A Case Report.

Echinococcus granulosus has been described as the common etiology of hydatid cysts in many parts of the world. A 54-yr-old female with lower abdominal pain referred to Gynecology Ward of Sari Imam Khomeini Hospital, Iran in 2016. Sonography was carried out and cysts in ovaries and liver were observed. The cysts of liver seemed to be hydatidosis but physicians were suspected about ovarian cystic mass. Anti-Echinococcus antibodies (ELISA) screen was positive. The operation was done on her and treatment by albendazole started one week before surgery and continued after discharge from the hospital. Pathology confirmed hydatidosis in ovary, also patient follow-up was performed for three months by abdominal CT scan that showed peritoan full of many small hydatid cysts. Uncommon locations for constitution of hydatid cysts such as ovary and peritoan often make the diagnosis very difficult. Hydatidosis is considered in differential diagnosis of any cysts of the entire body, especially in endemic countries such as Iran.

Evaluation of E-cadherin Expression in Gastric Cancer and Its Correlation with Clinicopathologic Parameters.

Background: Gastric cancer is one of the most common cancers in the world. There are many genomic and molecular factors that cause gastric cancer to occur. Also, many markers that associate with tumor invasiveness have been known. E-cadherin is a calcium- mediated cell adhesion molecule. In some studies, abnormal expression of E-cadherin has been seen in gastric carcinoma. However, in the studies done there has been some conflicting information about abnormal expression of this marker in a variety of gastric carcinoma and also about the expression of this marker and its correlation with various clinicopathologic factors of tumor. Subjects andMethods: A case control study was performed on total or partial gastrectomy tissue samples obtained from 70 patients with gastric cancer and adjacent non-neoplastic tissues. The immunohistochemistry was used to assess E-cadherin expression. The correlation between abnormal E-cadherin expression and tumor histopathology was evaluated in all patients. Results: Among 70 patients who were analyzed, 48.6% showed abnormal E-cadherin expression. A significant correlation was seen between abnormal E-cadherin expression and tumor stage, grade, lymph node metastasis, tumor phenotype, tumor type, depth of invasion and age. Conclusion: Abnormal E-cadherin expression is a common phenomenon in gastric cancer. Because there was a strong correlation between abnormal E-cadherin expression and tumor stage, tumor grade, depth of invasion and regional lymph node involvement, this marker may be used as a predictive factor for tumor invasiveness in gastric cancer.

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.

Human Epidermal Growth Factor Receptor Expression in Colorectal Cancer and Its Relationship with Clinicopathological Characteristics.

BACKGROUND Some recent studies reported human epidermal growth factor receptor (HER-2/neu) as a marker that can be used in immunological studies of colorectal carcinoma for predicting the prognosis and the treatment. Therefore, we aimed to investigate the frequency of HER-2 expression in patients with colorectal cancer, and explore the relationship between clinicopathological prognostic factors and its expression based on immunohistochemical analysis. METHODS This study included 50 patients with a histologically proven diagnosis of colorectal carcinoma who received surgery at Imam Khomeini Hospital affiliated to Mazandaran University of Medical Sciences. First, HER-2/neu protein expressions were detected by immunohistochemistry and then the data extracted from recorded files. RESULTS The median age of the patients was 60.2±13.9 years (range: 25-93 years). There was no significant relationship between size of tumor, age, sex, lymph node metastases, distant metastasis, differentiation, and stage of the disease with positive expression of HER-2 in this study. CONCLUSION No significant relationship between expression of HER-2 and clinicopathological prognostic factors was found in our study. Further comprehensive and prospective trial with standard method to evaluate the role of HER-2 expression among patients with colorectal cancer is needed.

Disseminated Strongyloidiasis in an Iranian Immunocompromised Patient: A Case Report.

Strongyloides stercoralis is a soil-transmitted helminth (STH) widespread in various part of the world. A 78-yr-old peasant diabetic female from Mazandaran Province northern Iran, was admitted to Infection Department of the Razi Hospital in city of Qaemshahr, north of Iran complaining about abdominal skin rash, pruritus, itching, anorexia, nausea, vomiting, dysuria and cough. This patient had cutaneous migration effects of S. stercoralis larvae in her abdominal skin (larva currents and urticaria). Lung CT without contrast demonstrate s bilateral diffuse ground glass opacity draws attention. Upper gastrointestinal endoscopy revealed gastro esophageal reflux with antral gastritis. Duodenal endoscopy showed unusual mucosa and a biopsy from it sent to the pathology laboratory. Histopathology of duodenal bulb and duodenum biopsy showed mild villous atrophy and S. stercoralis infection. The patient was treated with albendazole and clinical sings improved completely after treatment. Strongyloidiasis should be carefully considered by clinicians who practice in endemic areas. Clinicians must keep a high level of skepticism for patients from endemic area.

Coinfection of Pulmonary Hydatid Cyst and Aspergilloma: Case Report and Systematic Review.

Aspergilloma infection consists of a mass of fungal hyphae, inflammatory cells, fibrin, mucus, and tissue debris and can colonize lung cavities due to underlying diseases such as tuberculosis, sarcoidosis, bronchiectasis, cavitary lung cancer, neoplasms, ankylosing spondylitis, bronchial cysts, and pulmonary infarction. Here we report coinfection of pulmonary hydatid cyst and aspergilloma in a 34-year-old female who had had history of minor thalassemia and suffered from chest pain, dyspnea, non-productive cough for at least five months, and hemoptysis for 20 days. Radiographic sign showed a large cavitary lesion (5 × 6 × 6 cm) involving left lower lobe (LLL). Dichotomous septate hyphae were observed in bronchoalveolar lavage and biopsy specimens from LLL. The patient subsequently improved after combined anti-helminth therapies with albendazole (400 mg/bd) and lobectomy. According to morphological and molecular characterization, Aspergillus niger was confirmed. In vitro antifungal susceptibility tests revealed that the MIC values for the antifungals used in this case in increasing order were posaconazole (0.125 µg/ml), itraconazole and voriconazole (0.5 µg/ml), and amphotericin B (1 µg/ml). The minimum effective concentration for caspofungin was 0.125 µg/ml. Subsequently, we systematically reviewed 22 confirmed cases of pulmonary hydatid cyst and aspergilloma during a period of 19 years (1995-2014) and discussed the epidemiology, clinical features, and treatment of this disease.

Application of hollow fiber liquid phase microextraction and dispersive liquid-liquid microextraction techniques in analytical toxicology.

The recent developments in hollow fiber liquid phase microextraction and dispersive liquid-liquid microextraction are reviewed. Applications of these newly emerging developments in extraction and preconcentration of a vast category of compounds including heavy metals, pesticides, pharmaceuticals and abused drugs in complex matrices (environmental and biological matrices) are reviewed and discussed. The new developments in these techniques including the use of solvents lighter than water, ionic liquids and supramolecular solvents are also considered. Applications of these new solvents reduce the use of toxic solvents and eliminate the centrifugation step, which reduces the extraction time.

Sunitinib Induced Immune Thrombocytopenia.

Sunitinib is an oral tyrosine kinase inhibitor which prevents tumor growth and metastatic progression. It was approved for treatment of advanced renal cell cancer, gastrointestinal stromal tumor and advanced pancreatic neuroendocrine tumors. It has several adverse reactions on multi organ systems including hematologic system. Although the neutropenia and thrombocytopenia commonly happens as Grade 3 or 4 abnormalities following bone marrow suppression, in the rare cases, the immune mediated abnormality may drive the sunitinib-induced hematologic disorder. In this report, we present a case of immune-mediated thrombocytopenia induced by sunitinib. One month after first treatment cycle with sunitinib, leucopenia and thrombocytopenia were occurred. The patient had a normal bone marrow aspiration and biopsy, the thrombocytopenia was resistant to platelet transfusion which successfully was treated with prednisolone.

Simultaneous Esophageal Squamous Cell Carcinoma and Adenocarcinoma: A Case Report.

Esophageal squamous cell carcinoma is a rather common cancer in northern Iran. Incidence of adenocarcinoma of esophagus has an increasing trend in Iran. Co-existence of both cancers in one patient is very rare. We report a middle age woman from northern Iran with a typical presentation of esophageal cancer, who was found to have a dual esophageal cancer. The disease was found in the advanced stage with pulmonary metastasis at the presentation. Palliative chemo-radiotherapy induced partial clinical response.

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.

Antinociceptive activity and effect of methanol extracts of three salvia spp. On withdrawal syndrome in mice.

PURPOSE: There are several reports about effects of Salvia spp. on CNS. The present experiment is undertaken to study effect of S. limbata, S. hypoleuca and S. macrosiphon on withdrawal syndrome in mice. METHODS: Antinociceptive activities of aerial parts of Salvia spp. is investigated using hot plate method. In addition, the effect of its aerial parts on morphine dependence is investigated in mice. After induction of morphine dependency, different concentrations of plant extract are injected. To assess morphine withdrawal, naloxone (5 mg kg-1, i.p.) are injected into mice on the 5th day. Withdrawal syndrome is assessed by placing each mouse in a glass box 30 cm in height and recording the incidence of escape jumps for 60 minutes. RESULTS: A decrease in incidence of escape jumps is observed in morphine dependence mice. S. limbata and S. hypoleuca extracts produced a statistically significant inhibition of pain induced by hot plate latency at (500, 1000 and 1500 mg kg-1) i.p. A significant increase in pain threshold is observed after 30 and 60 minutes (p < 0.001). The activity was comparable to that of morphine (30 mg kg-1, i.p., p > 0.05). The antinociceptive activity increased up to 60 minutes. CONCLUSION: S. limbataand S. hypolecuca extracts produced statistically significant inhibition of pain and development of morphine dependence in mice.

Study of the Hepatoprotective Activity of Methanolic Extract of Feijoa sellowiana Fruits Against MDMA using the Isolated Rat Liver Perfusion System.

liver injury induced by viruses, chemicals and drugs can be protected by different medicinal plants. Feijoa sellowiana (Myrtaceae) is an evergreen bush native to southern areas of South America, as well as Iran where the fruits are very popular. Feijoa has shown a potent antimicrobial effect. Morever, the antioxidant activity of total Feijoa extract has also been reported. MDMA or ecstasy is a ring-substituted amphetamine derivative which has been abused as a widespread recreational drug by the young generation. Liver is a target organ for MDMA toxicity. In fact, this sense MDMA is metabolized by cytochromes P4502D, 2B and 3Aand reactive metabolites are readily oxidized to the corresponding o-qiuinones and reactive oxygen species (ROS). This study investigated whether methanilic Feijoa sellowiana fruits can produce biochemical changes using the Isolated Rat Liver Perfusion (IRLP) system. The, the liver was perfused with different concentrations of the extract (10, 20, 40, 50,100 mg/kg), added to the buffer and perfused within 2 h. During the perfusion we tried to find out the antioxidant activity or liver protective effect of Feijoa, by determinining amino-transferases activities (SGOT and SGPT ) and glutathione reductase (GSH) level in comparison with the positive and negative controls. Subsequently, sections of liver tissue were examined for any histopathological changes. The results revealed that the activities of SGOT and SGPT were seriously decreased and GSH level was significantly increased by the Feijoa extract. Overall, necrosis in the liver parenchyma was decreased. These findings revealed that Feijoa sellowiana is an effective hepatoprotective plant.