Search results for: cancerous tumor

Authors: Habib Alah Dadgar, Nasim Norouzbeigi

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The precise definition margin of high and low-grade gliomas is crucial for treatment. We aimed to assess the feasibility of assessment of the resection legions with post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET). Four patients with the suspicion of high and low-grade were enrolled. Patients underwent post-operative [18F]FET-PET, pre-operative magnetic resonance imaging (MRI) and CT for clinical evaluations. In our study, three patients had negative response to recurrence and progression and one patient indicated positive response after surgery. [18F]FET-PET revealed a legion of increased radiotracer uptake in the dura in the craniotomy site for patient 1. Corresponding to the patient history, the study was negative for recurrence of brain tumor. For patient 2, there was a lesion in the right parieto-temporal with slightly increased uptake in its posterior part with SUVmax = 3.79, so the study was negative for recurrence evaluation. In patient 3 there was no abnormal uptake with negative result for recurrence of brain tumor. Intense radiotracer uptake in the left parietal lobe where in the MRI there was a lesion with no change in enhancement in the post-contrast image is indicated in patient 4. Assessment of the resection legions in high and low-grade gliomas with [18F]FET-PET seems to be useful.

Keywords: FET-PET, CT, glioma, MRI

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Authors: Yousry El-Sayed Elbolkiny, Mohamed Labib Salem

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Background: Rosemary (ROLE) and costus (SLRE) have been established to show antioxidant effects. Aim: This study aimed to evaluate the ameliorating effects of ROLE and SLRE on the side effects induced by cisplatin (CIS) in tumor-bearing mice. Materials and Methods: Extracts of ROLE and SLRE were examined for their phytochemical activities. To evaluate their anti-tumor effects, mice were inoculated intraperitoneally (i.p.) with 2.5x105 Ehrlich ascites carcinoma (EAC) and then treated i.p. with CIS at days 3-7 and with ROLE (dose) or SLRE (dose) at days 3-14. Mice were sacrificed on day 14 for CBC and T-cell analyses. Results: Phytochemical analysis revealed that both ROLE and SLRE showed similar antioxidant activities. Treatment of EAC-bearing mice with CIS-induced antitumor efficacy of about 90%. Treatment with CIS in combination with ROLE or SLRE did not further enhance the antitumor activity of CIS. However, co-administration of ROLE or SLRE with CIS significantly increased the antitumor efficacy of CIS. Flow cytometric analysis showed that the numbers of CD4+ and CD8+ T cells were decreased in EAC-bearing mice after treatment with CIS. Treatment with both ROLE and SLRE improved the number of these cells. Conclusion: Combinatorial treatment with rosemary and costus can enhance the antitumor activity of CIS

Keywords: CBC, cisplantin, costus, rosemary

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Authors: Michael Aupetit, Mahmoud Al-ismail, Khaled Mohamed

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Cancer is a major public health problem all over the world. Breast cancer has the highest incidence rate over all cancers for women in Qatar making its study a top priority of the country. Human cancer is a dynamic disease that develops over an extended period through the accumulation of a series of genetic alterations. A Darwinian process drives the tumor cells toward higher malignancy growing the branches of a progression tree in the space of genes expression. Although it is not possible to track these genetic alterations dynamically for one patient, it is possible to reconstruct the progression tree from the aggregation of thousands of tumor cells’ genetic profiles from thousands of different patients at different stages of the disease. Analyzing the progression tree is a way to detect pivotal molecular events that drive the malignant evolution and to provide a guide for the development of cancer diagnostics, prognostics and targeted therapeutics. In this work we present the development of a Visual Analytic web platform CanVis enabling users to upload gene-expression data and analyze their progression tree. The server computes the progression tree based on state-of-the-art techniques and allows an interactive visual exploration of this tree and the gene-expression data along its branching structure helping to discover potential driver genes.

Keywords: breast cancer, progression tree, visual analytics, web platform

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Authors: Sabine Danzinger, Nora Hielscher, Miriam Izso, Johanna Metzler, Carmen Trinkl, Christian Pfeifer, Kristina Tendl-Schulz, Christian F. Singer

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The objective of this study is to analyze the characteristics of invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC) and to investigate the impact of histology on axillary lymph node (ALN) involvement in luminal A subtype tumors. Methods: We retrospectively analyzed patients diagnosed with ILC or IDC from 2012 to 2016 who underwent surgery. Patients constituted 493 primary early breast cancer cases (82 ILC; 411 IDC). Results: Compared with IDC, ILC tumors were significantly more likely to be grade 2, estrogen receptor- (ER) positive (þ), have a lower proliferation rate (Ki67 <14%), and a higher patholog- ical T stage (pT2–4). The luminal A subtype was significantly more common in ILC compared with IDC. In a multivariate regression model, grade 2, ERþ, progesterone receptor-positive, pT2, and pT3 were significantly associated with ILC. Additionally, with the luminal A subtype, ALN involvement (pathological node stage (pN)1–3) was significantly more frequent with ILC versus IDC. Conclusions: Our data suggests that grade 2, positive hormone receptor status, and higher pathological T stage are associated with ILC. With the luminal A subtype, ALN involvement was more frequent with ILC versus IDC.

Keywords: breast cancer, lobular histology, tumor biology, hormone receptor, ki67

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Authors: Roudabeh Vakil Monfared, Farhad Mashayekhi

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Breast cancer is the most common malignancy type among women with about 1 million new cases each year. The immune system plays an important role in the breast cancer development. OX40L (also known as TNFSF4), a membrane protein, which is a member of the tumor necrosis factor super family binds to its receptor OX40 and this co-stimulation has a crucial role in T-cell proliferation, survival and cytokine release. Due to the importance of the T-cells in anti-tumor activities of OX40L we studied the association of rs3850641 (T→C) polymorphism of OX40L gene with breast cancer. The study included 123 women with breast cancer and 126 healthy volunteers with no signs of cancer. Genomic DNA was extracted from blood leucocytes. Genotype and allele frequencies were determined in patients and control cases with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the analysis was performed by Med Calc. The prevalence of genotype frequencies of TT, CT and CC were 60.9%, 30.08% and 8.9 % in patients with breast cancer and 74.6 %, 18.25 % and 7.14 % in healthy volunteers while the T and C allelic frequency was 76.01% and 23.98 % in patients and 83.73% and 16.26% in healthy controls. Respectively Statistical analysis has shown no significant difference from the comparison of either genotype (P=0.06). According to these results, the rs3850641 SNP has no association with the susceptibility of breast cancer in a population in northern Iran. However, further studies in larger populations including other genetic and environmental factors are required to achieve conclusion.

Keywords: OX40L, gene, polymorphism, breast cancer

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

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Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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Authors: Naif Al-Jomah, Falah H Al-Mohanna, Abdelilah Aboussekhra

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Active breast cancer-associated fibroblasts (CAFs), the most influential cells in breast tumor microenvironment, express/secrete high levels of the proinvasive/metastatic interleukin-6 (IL-6). Therefore, we have tested here the effect of the IL-6 receptor (IL-6R) inhibitor tocilizumab (TCZ; Actemra) on different active breast CAFs. We have shown that TCZ potently and persistently suppresses the expression of various CAF biomarkers, namely α-SMA, SDF-1 as well as the STAT3 pathway and its downstream target AUF1. TCZ also inhibited the proliferation, migration and invasion abilities of active breast CAF cells. Additionally, TCZ repressed the ability of CAF cells in promoting epithelial-to-mesenchymal transition, and enhancing the migratory/invasive and proliferative capacities of breast cancer cells in vitro. Importantly, these findings were confirmed in orthotopic humanized breast tumors in mice. Furthermore, TCZ suppressed the expression of the pro-angiogenic factor VEGF-A and its transactivator HIF-1α in CAF cells, and consequently inhibited the angiogenic-promoting effect of active CAFs both in vitro and in orthotopic tumor xenografts. These results indicate that inhibition of the IL-6/STAT3/AUF1 pathway by TCZ can normalize active breast CAFs and suppress their paracrine pro-carcinogenic effects, which paves the way toward development of specific CAF-targeting therapy, badly needed for more efficient breast cancer treatments.

Keywords: angiogenesis, interleukin-6, paracrine, cancer-associated fibroblasts

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Authors: J. Visser, C. Driver, T. Ebenhan

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[¹⁸F]-FDG (fluorodeoxyglucose) is a radiopharmaceutical compound that is used for non-invasive cancer tumor imaging through positron emission tomography (PET). This radiopharmaceutical is used to visualise the metabolic processes in tumour tissues, which can be applied for the diagnosis and prognosis of various types of cancer. [¹⁸F]-FDG has widespread use in both clinical and pre-clinical research settings. Imaging using [¹⁸F]-FDG results in representative normal tissue distribution as well as visualisation of hypermetabolic lesions ([¹⁸F]-FDG avid foci). The metabolic tissue concentration of these lesions following [¹⁸F]-FDG administration can be quantified using Standard Uptake Values (SUV). Standard uptake values of [¹⁸F]-FDG-based Positron Emission Tomography can be influenced by various biological and technical handling factors. Biological factors that affect [¹⁸F]-FDG uptake include the blood glucose levels of subjects, normal physiological variants between subjects and administration of certain pharmaceutical agents. Technical factors that can have an effect include the route of radiopharmaceutical or pharmaceutical agents administered and environmental conditions such as ambient temperature and lighting. These factors influencing tracer uptake need to be investigated to improve the robustness of the imaging protocol, which will achieve reproducible image acquisition across various research projects, optimised tumor visualisation and increased data validity and reliability.

Keywords: fluorodeoxyglucose, tumour imaging, Rodent, Blood Glucose, PET/CT Imaging

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Authors: Meenakshi Barsaul Chauhan, Aastha Chauhan, Shilpa Hurmade, Rajeev Sen, Jyotsna Sen, Monika Dalal

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Introduction: Ovarian masses are common forms of neoplasm in women and represent 2/3rd of gynaecological malignancies. A pre-operative suggestion of malignancy can guide the gynecologist to refer women with suspected pelvic mass to a gynecological oncologist for appropriate therapy and optimized treatment, which can improve survival. In the younger age group preoperative differentiation into benign or malignant pathology can decide for conservative or radical surgery. Imaging modalities have a definite role in establishing the diagnosis. By using International Ovarian Tumor Analysis (IOTA) classification with sonography, costly radiological methods like Magnetic Resonance Imaging (MRI) / computed tomography (CT) scan can be reduced, especially in developing countries like India. Thus, this study is being undertaken to evaluate the role of clinical methods and sonography for diagnosis of the nature of the ovarian tumor. Material And Methods: This prospective observational study was conducted on 40 patients presenting with ovarian masses, in the Department of Obstetrics and Gynaecology, at a tertiary care center in northern India. Functional cysts were excluded. Ultrasonography and color Doppler were performed on all the cases.IOTA rules were applied, which take into account locularity, size, presence of solid components, acoustic shadow, dopper flow etc . Magnetic Resonance Imaging (MRI) / computed tomography (CT) scans abdomen and pelvis were done in cases where sonography was inconclusive. In inoperable cases, Fine needle aspiration cytology (FNAC) was done. The histopathology report after surgery and cytology report after FNAC was correlated statistically with the pre-operative diagnosis made clinically and sonographically using IOTA rules. Statistical Analysis: Descriptive measures were analyzed by using mean and standard deviation and the Student t-test was applied and the proportion was analyzed by applying the chi-square test. Inferential measures were analyzed by sensitivity, specificity, negative predictive value, and positive predictive value. Results: Provisional diagnosis of the benign tumor was made in 16(42.5%) and of the malignant tumor was made in 24(57.5%) patients on the basis of clinical findings. With IOTA simple rules on sonography, 15(37.5%) were found to be benign, while 23 (57.5%) were found to be malignant and findings were inconclusive in 2 patients (5%). FNAC/Histopathology reported that benign ovarian tumors were 14 (35%) and 26(65%) were malignant, which was taken as the gold standard. The clinical finding alone was found to have a sensitivity of 66.6% and a specificity of 90.9%. USG alone had a sensitivity of 86% and a specificity of 80%. When clinical findings and IOTA simple rules of sonography were combined (excluding inconclusive masses), the sensitivity and specificity were 83.3% and 92.3%, respectively. While including inconclusive masses, sensitivity came out to be 91.6% and specificity was 89.2. Conclusion: IOTA's simple sonography rules are highly sensitive and specific in the prediction of ovarian malignancy and also easy to use and easily reproducible. Thus, combining clinical examination with USG will help in the better management of patients in terms of time, cost and better prognosis. This will also avoid the need for costlier modalities like CT, and MRI.

Keywords: benign, international ovarian tumor analysis classification, malignant, ovarian tumours, sonography

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Authors: Liu Xiaohan

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Epstein–Barr virus (EBV) is a human herpesvirus and is closely related to many malignancies of lymphocyte and epithelial origins, such as gastric cancer, Burkitt’s lymphoma, and nasopharyngeal carcinoma (NPC). NPC is a malignant epithelial tumor which is 100% associated with EBV latent infection. Most of the NPC cases are densely populated in southern China, especially in Guangdong and Hong Kong. To our knowledge, overexpression of pro-inflammatory cytokines may result in a loss of balance of the immune system and cause damage to human bodies. Interleukin-6 (IL6) is a pro-inflammatory cytokine which plays an important role in tumor progression. In addition, gene expression is regulated by both transcriptional and post-transcriptional pathways, while post-transcriptional regulation is an important mechanism to modulate the mature mRNA level in mammalian cells. AU-rich element binding factor 1 (AUF1)/heterogeneous nuclear RNP D (hnRNP D) is known for its function in destabilizing mRNAs, including cytokines and cell cycle regulators. Previous studies have found that overexpression of hnRNP D would lead to tumorigenesis. In this project, our aim is to determine the role played by hnRNP D in EBV-infected cells and how our anti-EBV agents can affect the function of hnRNP D. The results of this study will provide a new insight into how the pro-inflammatory cytokine expression can be regulated by EBV.

Keywords: interleukin 6 (IL6), epstein-barr virus (EBV), nasopharyngeal carcinoma (NPC, epstein-barr nuclear antigen-1 (EBNA1)

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Authors: Sundaresan Sivapatham, B. Prabhu

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Cancer results from a multistage, multi-mechanism carcinogenesis process that involves mutagenic, cell death and epigenetic mechanisms, during the three distinguishable but closely allied stages: initiation, promotion, and progression. Chemoprevention is promising in the realm of cancer prevention and it has been shown to reduce the risk of development of carcinoma in highly susceptible individuals such as those with known genetic mutations or high level of risk factors. The present study is aimed at the need of early detection of bladder cancer in order to improve performance in the treatment of this disease. Consumption of certain natural products like DIM is associated with a reduction in cancer incidence in humans. The study showed the protective effects of Diindolylmethane in N-Butyl-N-(4-hydroxybutyl) nitrosamine treated rats. Results of the study had shown the changes in the tumor markers, biomarkers and histopathological alterations in experimental rats when compared to control rats. The protective effects of DIM were shown from the results of cell proliferation, apoptotic markers and histopathological findings when compared with experimental control animals. Hence, our results speculate that the tumor markers, apoptotic markers, histopathological changes and cell proliferation index measured as PCNA serves as an indicator suggestive of protective effects of DIM in BBN induced urinary bladder carcinogenesis.

Keywords: bladder cancer, N-Butyl-N-(4-hydroxybutyl) nitrosamine, diindolylmethane, histopathology

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Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

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Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

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Authors: Mustafa M. Donma, Orkide Donma

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Iron is physiologically essential. However, it also participates in the catalysis of free radical formation reactions. Its deficiency is associated with amplified health risks. This trace element establishes some links with another physiological process related to cell death, apoptosis. Both iron deficiency and iron overload are closely associated with apoptosis. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) has the ability to trigger apoptosis and plays a dual role in the physiological versus pathological inflammatory responses of tissues. The aim of this study was to investigate the status of these parameters as well as the associations among them in children with obesity, a low-grade inflammatory state. The study was performed on groups of children with normal body mass index (N-BMI) and obesity. Forty-three children were included in each group. Based upon age- and sex-adjusted BMI percentile tables prepared by World Health Organization, children whose values varied between 85 and 15 were included in N-BMI group. Children whose BMI percentile values were between 99 and 95 comprised obese (OB) group. Institutional ethical committee approval and informed consent forms were taken prior to the study. Anthropometric measurements (weight, height, waist circumference, hip circumference, head circumference, neck circumference) and blood pressure values (systolic blood pressure and diastolic blood pressure) were recorded. Routine biochemical analysis including serum iron, total iron binding capacity (TIBC), transferrin saturation percent (Tf Sat %), and ferritin were performed. Soluble tumor necrosis factor-like weak inducer of apoptosis levels were determined by enzyme-linked immunosorbent assay. Study data was evaluated using appropriate statistical tests performed by the statistical program SPSS. Serum iron levels were 91±34 mcrg/dl and 75±31 mcrg/dl in N-BMI and OB children, respectively. The corresponding values for TIBC, Tf Sat %, ferritin were 265 mcrg/dl vs 299 mcrg/dl, 37.2±19.1 % vs 26.7±14.6 %, and 41±25 ng/ml vs 44±26 ng/ml. in N-BMI and OB groups, sTWEAK concentrations were measured as 351 ng/L and 325 ng/L, respectively (p>0.05). Correlation analysis revealed significant associations between sTWEAK levels and iron related parameters (p<0.05) except ferritin. In conclusion, iron contributes to apoptosis. Children with iron deficiency have decreased apoptosis rate in comparison with that of healthy children. sTWEAK is inducer of apoptosis. Obese children had lower levels of both iron and sTWEAK. Low levels of sTWEAK are associated with several types of cancers and poor survival. Although iron deficiency state was not observed in this study, the correlations detected between decreased sTWEAK and decreased iron as well as Tf Sat % values were valuable findings, which point out decreased apoptosis. This may induce a proinflammatory state, potentially leading to malignancies in the future lives of obese children.

Keywords: apoptosis, children, iron-related parameters, obesity, soluble tumor necrosis factor-like weak inducer of apoptosis

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Authors: Tuong Thi Van Thuy, Dao Van Toan, Nguyen Duc Phuc

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Mesenchymal stem cells (MSCs) were discovered in the 1970s with their unique properties of differentiation, immunomodulation, multiple secreting, and homing factors to injured organs. MSC-based therapies have emerged as a promising strategy for various diseases such as cancer, tissue regeneration, or immunologic/inflammatory-related diseases. This study evaluated the clinical application of MSCs for cancer therapy in trials registered on Clinical Trial as of July 2022. The results showed 40 clinical trials used MSCs in various cancer conditions. 62% of trials used MSCs for therapeutic purposes to minimize the side effects of cancer treatment. Besides, 38% of trials were focused on using MSCs as a therapeutic agent to treat cancer directly. Most trials (38/40) are ongoing phase I/II, and 2 are entering phase III. 84% of trials used allogeneic MSCs compared with 13% using autologous sources and 3% using both. 25/40 trials showed participants received a single dose of MSCs, while the most times were 12 times in a pancreatic cancer treatment trial. Conclusion: MSC-based therapy for cancer in clinical trials should be applied to (1) minimize the side effects of oncological treatments and (2) directly affect the tumor via selectively delivering anti-cancer payloads to tumor cells. Allogeneic MSCs are a priority selected in clinical cancer therapy.

Keywords: mesenchymal stem cells, MSC-based therapy, cancer condition, cancer treatment, clinical trials

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Authors: Aoxue Yang, Weili Tian, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Glucocorticoids (GCs) are used to treat GBM-associated edema. However, glucocorticoids participate in the physiological response to psychosocial stress, linked to poor cancer prognosis. This raises concern that glucocorticoids affect the tumor and BTSCs. Identifying markers specifically expressed by brain tumor stem cells (BTSCs) may enable specific therapies that spare their regular tissue-resident counterparts. By ribosome profiling analysis, we have identified that glycerol-3-phosphate dehydrogenase 1 (GPD1) is expressed by dormant BTSCs but not by NSCs. Through different stress-induced experiments in vitro, we found that only dexamethasone (DEXA) can significantly increase the expression of GPD1 in NSCs. Adversely, mifepristone (MIFE) which is classified as glucocorticoid receptors antagonists, could decrease GPD1 protein level and weaken the proliferation and stemness in BTSCs. Furthermore, DEXA can induce GPD1 expression in tumor-bearing mice brains and shorten animal survival, whereas MIFE has a distinct adverse effect that prolonged mice lifespan. Knocking out GR in NSC can block the upregulation of GPD1 inducing by DEXA, and we find the specific sequences on GPD1 promotor combined with GR, thus improving the efficiency of GPD1 transcription from CHIP-Seq. Moreover, GR and GPD1 are highly co-stained on GBM sections obtained from patients and mice. All these findings confirmed that GR could regulate GPD1 and loss of GPD1 Impairs Multiple Pathways Important for BTSCs Maintenance GPD1 is also a critical enzyme regulating glycolysis and lipid synthesis. We observed that DEXA and MIFE could change the metabolic profiles of BTSCs by regulating GPD1 to shift the transition of cell dormancy. Our transcriptome and lipidomics analysis demonstrated that cell cycle signaling and phosphoglycerides synthesis pathways contributed a lot to the inhibition of GPD1 caused by MIFE. In conclusion, our findings raise concern that treatment of GBM with GCs may compromise the efficacy of chemotherapy and contribute to BTSC dormancy. Inhibition of GR can dramatically reduce GPD1 and extend the survival duration of GBM-bearing mice. The molecular link between GPD1 and GR may give us an attractive therapeutic target for glioblastoma.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides

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Authors: Shiva Naidoo, Kristena Yossef, Grimm Jimm, Mirza Wasique, Eric Kemmerer, Joshua Obuch, Anand Mahadevan

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Background: Fiducial markers effectively enhance tumor target visibility prior to Stereotactic Body Radiation Therapy or Proton therapy. To streamline clinical practice, fiducial placement guidelines from a robotic radiosurgery vendor were examined with the goals of optimizing and standardizing feasible geometries for each treatment indication. Clinical examples of prostate, renal, and pancreatic cases are presented. Methods: Vendor guidelines (Accuray, Sunnyvale, Ca) suggest implantation of 4–6 fiducials at least 20 mm apart, with at least a 15-degree angular difference between fiducials, within 50 mm or less from the target centroid, to ensure that any potential fiducial motion (e.g., from respiration or abdominal/pelvic pressures) will mimic target motion. Also recommended is that all fiducials can be seen in 45-degree oblique views with no overlap to coincide with the robotic radiosurgery imaging planes. For the prostate, a standardized geometry that meets all these objectives is a 2 cm-by-2 cm square in the coronal plane. The transperineal implant of two pairs of preloaded tandem fiducials makes the 2 cm-by-2 cm square geometry clinically feasible. This technique may be applied for renal cancer, except repositioned in a sagittal plane, with the retroperitoneal placement of the fiducials into the tumor. Pancreatic fiducial placement via endoscopic ultrasound (EUS) is technically more challenging, as fiducial placement is operator-dependent, and lesion access may be limited by adjacent vasculature, tumor location, or restricted mobility of the EUS probe in the duodenum. Fluoroscopically assisted fiducial placement during EUS can help ensure fiducial markers are deployed with optimal geometry and visualization. Results: Among the first 22 fiducial cases on a newly installed robotic radiosurgery system, live x-ray images for all nine prostatic cases had excellent fiducial visualization at the treatment console. Renal and pancreatic fiducials were not as clearly visible due to difficult target access and smaller caliber insertion needle/fiducial usage. The geometry of the first prostate case was used to ensure accurate geometric marker placement for the remaining 8 cases. Initially, some of the renal and pancreatic fiducials were closer than the 20 mm recommendation, and interactive feedback with the proceduralists led to subsequent fiducials being too far to the edge of the tumor. Further feedback and discussion of all cases are being used to help guide standardized geometries and achieve ideal fiducial placement. Conclusion: The ideal tradeoffs of fiducial visibility versus the thinnest possible gauge needle to avoid complications needs to be systematically optimized among all patients, particularly in regards to body habitus. Multidisciplinary collaboration among proceduralists and radiation oncologists can lead to improved outcomes.

Keywords: fiducial, prostate cancer, renal cancer, pancreatic cancer, radiotherapy

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Authors: M. Sunitha, B. Nithyavani, Mathew Yohannan, S. Thiruvieni Balajji, M. A. Rathi, C. Arul Raj, P. Ragavendran, V. K. Gopalkrishnan

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Establishment of an early and reliable biomarker for ovarian carcinogenesis whose expression can be monitored through noninvasive techniques will enable early diagnosis of cancer. Carbonic anhydrases (CA) isozymes IX and XII have been suggested to play a role in oncogenic processes. In von Hippel-Lindau (VHL)-defective tumors, the cell surface transmembrane carbonic anhydrase (CA) CA XI and CA XII genes are overexpressed because of the absence of pVHL. These enzymes are involved in causing a hypoxia condition, thereby providing an environment for metastasis. Aberrant expression of the facilitative glucose transporter GLUT I is found in a wide spectrum of epithelial malignancies. Studying the mRNA expression of CA IX, CA XII and Glut I isozymes in ovarian cancer cell lines (OAW-42 and PA-1) revealed the expression of these hypoxia genes. Immunohistochemical staining of carbonic anhydrases was also performed in 40 ovarian cancer tissues. CA IX and CA XII were expressed at 540 bp and 520 bp in OAW42, PA1 in ovarian cancer cell lines. GLUT-1 was expressed at 325bp in OAW 42, PA1 genes in ovarian cancer cell lines. Immunohistochemistry revealed high to moderate levels of expression of these enzymes. The immuostaining was seen predominantly on the cell surface membrane. The study concluded that these genes CA IX, CA XII and Glut I are expressed under hypoxic condition in tumor cells. From the present results expression of CA IX, XII and Glut I may represent potential targets in ovarian cancer therapy.

Keywords: ovarian cancer, carbonic anhydrase IX, XII, Glut I, tumor markers

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Authors: Deepak Kumar Mittal, Alok Kumar Jena, Deepmala Joshi

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The present study was carried out to observe the hepatoprotective effect and antioxidant activity of the aqueous extract of the roots of Polygonum bistorta (PB) (200 mg/kg) and Zingiber roseum (ZR) (250 mg/kg) in rats treated with carbon tetrachloride (0.15 ml/kg, i.p.). Extract of PB and ZR at the tested doses restored the levels of liver homogenate enzymes, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase enzymes, significantly. The activities of MTT assay significantly recovered the damage and supported the biochemical observations. This study suggests that Zingiber roseum has a higher protective effect on liver, compared to Polygonum bistorta, against carbon tetrachloride-induced hepatotoxicity and possesses antioxidant activities. Also, extracts exhibited moderate anticancer activity towards cell viability at higher concentration.

Keywords: Polygonum bistorta, Zingiber roseum, hepatoprotective effect, carbon tetrachloride, anti-cancerous

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Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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MicroRNAs (miRNAs) act as key regulators of multiple cancers. Hsa-miR-329 (miR-329) functions as a tumor suppressor in some malignancies. However, its role on lung cancer remains poorly understood. In this study, we investigated the role of miR-329 on the development of lung cancer. The results indicated that miR-329 was decreased in primary lung cancer tissues compared with matched adjacent normal lung tissues and very low levels were found in a non-small cell lung cancer (NSCLC) cell lines. Ectopic expression of miR-329 in lung cancer cell lines substantially repressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibiting cyclin D1, cyclin D2, and up-regulatiing p57(Kip2) and p21(WAF1/CIP1). In addition, miR-329 promoted NSCLC cell apoptosis, as indicated by up-regulation of key apoptosis gene cleaved caspase-3, and down-regulation of anti-apoptosis gene Bcl2. Moreover, miR-329 inhibited cellular migration and invasiveness through inhibiting matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene MET was revealed to be a putative target of miR-329, which was inversely correlated with miR-329 expression. Furthermore, down-regulation of MET by siRNA performed similar effects to over-expression of miR-329. Collectively, our results demonstrated that miR-329 played a pivotal role in lung cancer through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic MET.

Keywords: hsa-miRNA-329(miR-329), MET, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Shashank Patidar, Sumit Kumar, Atul Srivastava, Suneet Singh

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Present work is concerned with the numerical investigation of thermal response of biological tissues during laser-based photo-thermal therapy for destroying cancerous/abnormal cells with minimal damage to the surrounding normal cells. Light propagation through the biological sample is mathematically modelled by transient radiative transfer equation. In the present work, application of the Lattice Boltzmann Method is extended to analyze transport of short-pulse radiation in a participating medium.In order to determine the two-dimensional temperature distribution inside the tissue medium, the RTE has been coupled with Penne’s bio-heat transfer equation based on Fourier’s law by several researchers in last few years.

Keywords: lattice Boltzmann method, transient radiation transfer equation, dual phase lag model

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Authors: Shima Behzadi

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Background: In many human malignant tumors, microRNA expression is aberrant. This study investigates miR-141 as a prognostic marker in colorectal cancer with K-Ras mutation. Materials and methods: In this case-control study, 100 patients, mostly over the age of 50, who were diagnosed with colorectal cancer were selected. The pathology department of the Mostoufi Pathobiology and Genetics Laboratory in Tehran confirmed the presence of colorectal cancer in samples of paraffin-embedded colon tissue. The case group was composed of patients with codon 12 and 13 mutations in exon 2 of the K-Ras gene, while tumor samples of individuals without these mutations in exon 2 of the K-Ras gene were selected as the control group, with patient consent. The changes in the expression of miR-141 were examined in both groups. Results: The study found that 20% of the patients tested positive for codon 12 mutation, and 10% of patients had codon 13 mutation. As a result, in 30 cases, there was a higher level of miR-141 expression. The miR-141 gene expression level in K-Ras positive tumor samples was 1.5 times higher than its expression level in K-Ras negative samples. This increase in expression was statistically significant, with a p-value of less than 0.001, indicating that the observed results are highly statistically significant. Conclusion: The study revealed that the incidence of typical K-Ras gene mutations among the colorectal cancer patients in the sample matches the national average in Iran. Additionally, the expression of miR-141 can serve as a useful biomarker to aid in the prognosis of colorectal cancer.

Keywords: colorectal cancer, K-Ras gene, miR-141 marker, real time PCR, electrophoresis

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Authors: Mustafa Cam, Nedim Ongun, Ufuk Kutluana

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Introduction: Restless LegsSyndrome (RLS) is a common, under-recognized disorder disrupts sleep and diminishes quality of life (1). The most common conditions highly associated with RLS include renalfailure, iron and folic acid deficiency, peripheral neuropathy, pregnancy, celiacdisease, Crohn’sdiseaseandrarelymalignancy (2).Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficientanemic populations is unknown (2). We report here a case of RLS due to iron deficiency in the setting of neuroendocrinetumor. Report of Case: A 35 year-old man was referred to our clinic with general weakness, weight loss (10 kg in 2 months)and 2-month history of uncomfortable sensations in his legs with urge to move, partially relieved by movement. The symptoms were presented very day, worsening in the evening; the discomfort forced the patient to getup and walk around at night. RLS was severe, with a score of 22 at the International RLS ratingscale. The patient had no past medical history. The patient underwent a complete set of blood analyses and the following ab normal values were found (normal limitswithinbrackets): hemoglobin 9.9 g/dl (14-18), MCV 70 fL (80-94), ferritin 3,5 ng/mL (13-150). Brain and spinemagnetic resonance imaging was normal. The patient consultated with gastroenterology clinic and gastointestinal systemendoscopy was performed for theetiology of the iron deficiency anemia. After the gastricbiopsy, results allowed us to reach the diagnosis of neuroen docrine tumor and the patient referred to oncology clinic. Discussion: The first important consideration from this case report is that the patient was referred to our clinic because of his severe RLS symptoms dramatically reducing his quality of life. However, our clinical study clearly demonstrated that RLS was not the primary disease. Considering the information available for this patient, we believe that the most likely possibility is that RLS was secondary to iron deficiency, a very well-known and established cause of RLS in theliterature (3,4). Neuroendocrine tumors (NETs) are rare epithelial neoplasms with neuroendocrine differentiation that most commonly originate in the lungs and gastrointestinal tract (5). NETs vary widely in their clinical presentation; symptoms are often nonspecific and can be mistaken for those of other more common conditions (6). 50% of patients with reported disease stage have either regional or distant metastases at diagnosis (7). Accurate and earlier NET diagnosis is the first step in shortening the time to optimal care and improved outcomes for patients (8). The most important message from this case report is that RLS symptoms can sometimes be thesign of a life-threatening condition. Conclusion: Careful and complete collection of clinical and laboratory data should be carried out in RLS patients. Inparticular, if RLS onset coincides with weight loss and iron deficieny anemia, gastricendos copy should be performed. It is known about that malignancy is a rare etiology in RLS patients and to our knowledge; it is the first case with neuro endocrine tumor presenting with RLS.

Keywords: neurology, neuroendocrine tumor, restless legs syndrome, sleep

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Authors: Hossain A., Miah S., Ray P. K.

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Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.

Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer

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Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi

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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.

Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation

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Authors: Fawaz M. Abdullah, Abdulrahman M. Al-Ahmari, Madiha Rafaqat

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Laser ablation of any solid target in the liquid leads to fabricate nanoparticles (NPs) with metal or different compositions of materials such as metals, alloys, oxides, carbides, hydroxides. The fabrication of NPs in liquids based on laser ablation has grown up rapidly in the last decades compared to other techniques. Nowadays, laser ablation has been improved to prepare different types of NPs with special morphologies, microstructures, phases, and sizes, which can be applied in various fields. The paper reviews and highlights the different sizes, shapes and application field of nanoparticles that are produced by laser ablation under different liquids and materials. Also, the paper provides a case study for producing a titanium NPs produced by laser ablation submerged in distilled water. The size of NPs is an important parameter, especially for their usage and applications. The size and shape have been analyzed by SEM, (EDAX) was applied to evaluate the oxidation and elements of titanium NPs and the XRD was used to evaluate the phase composition and the peaks of both titanium and some element. SEM technique showed that the synthesized NPs size ranges were between 15-35 nm which can be applied in various field such as annihilator for cancerous cell etc.

Keywords: nanoparticles, laser ablation, titanium NPs, applications

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Authors: Parveen Kundu, Nitika Chawla, Ruchi Agarwal, Swaran Kaur

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Background: Mature cystic teratoma is a benign, most common tumor of the ovary occurring mostly in young and middle-aged females. This study consists of 19 cases of mature cystic teratomas which were received in the Department Of Pathology over a period of two years. There were malignant transformations observed in three cases, which makes it very important for pathologists to thoroughly examine the entire specimen of mature cystic teratomas. Material and Methods: Nineteen reported cases of mature cystic teratomas were received in Deptt. Of Pathology, BPS GMC Khanpur Kalan, Sonepat, over a two-year period from November 2020 to October 2022 and reviewed retrospectively. Data regarding age, size, laterality, gross, morphological features, and surgery performed were retrieved from pathological archives. Results: In our study, the most common age of presentation was the 20-40 year age group. The most common presenting complaint was fullness in the abdomen or abdominal distension. Four out of 19 cases studied cases presented with bilateral ovarian cysts. Tumor size ranged from 6 to 20 cm in diameter. In seven cases, cysts were greater than or equal to 10 cm in diameter. Three cases showed malignant transformation. Conclusion: It is very important to thoroughly examine the contralateral ovary to rule out bilateral presentation. A furthermost thorough examination is advised in tumors of size >10 cm and in tumors with solid areas to rule out any malignant transformation.

Keywords: teratoma, ovary, malignant, transformation

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Authors: Ugo Rovigatti

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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.

Keywords: neuroblastoma, MYCN, amplification, viruses, GD2

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Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain

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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Keywords: sphingosomes, anti-cancer, doxorubicin, formulation

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Authors: Karen Boaz, C. R. Charan

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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.

Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity

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Authors: Nadia Obaed, Lexi Frankel, Amalia Ardeljan, Denis Nigel, Anniki Witter, Omar Rashid

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Breast cancer is the most common cancer among women, with a lifetime risk of one in eight of all women in the United States. Although breast cancer is prevalent throughout the world, the uneven distribution in incidence and mortality rates is shaped by the variation in population structure, environment, genetics and known lifestyle risk factors. Furthermore, the bacterial profile in healthy and cancerous breast tissue differs with a higher relative abundance of bacteria capable of causing DNA damage in breast cancer patients. Previous bacterial infections may change the composition of the microbiome and partially account for the environmental factors promoting breast cancer. One study found that higher amounts of Staphylococcus, Bacillus, and Enterobacteriaceae, of which Escherichia coli (E. coli) is a part, were present in breast tumor tissue. Based on E. coli’s ability to damage DNA, it is hypothesized that there is an increased risk of breast cancer associated with previous E. coli infection. Therefore, the purpose of this study was to evaluate the correlation between E. coli infection and the incidence of breast cancer. Holy Cross Health, Fort Lauderdale, provided access to the Health Insurance Portability and Accountability (HIPAA) compliant national database for the purpose of academic research. International Classification of Disease 9th and 10th Codes (ICD-9, ICD-10) was then used to conduct a retrospective analysis using data from January 2010 to December 2019. All breast cancer diagnoses and all patients infected versus not infected with E. coli that underwent typical E. coli treatment were investigated. The obtained data were matched for age, Charlson Comorbidity Score (CCI score), and antibiotic treatment. Standard statistical methods were applied to determine statistical significance and an odds ratio was used to estimate the relative risk. A total of 81286 patients were identified and analyzed from the initial query and then reduced to 31894 antibiotic-specific treated patients in both the infected and control group, respectively. The incidence of breast cancer was 2.51% and present in 2043 patients in the E. coli group compared to 5.996% and present in 4874 patients in the control group. The incidence of breast cancer was 3.84% and present in 1223 patients in the treated E. coli group compared to 6.38% and present in 2034 patients in the treated control group. The decreased incidence of breast cancer in the E. coli and treated E. coli groups was statistically significant with a p-value of 2.2x10-16 and 2.264x10-16, respectively. The odds ratio in the E. coli and treated E. coli groups was 0.784 and 0.787 with a 95% confidence interval, respectively (0.756-0.813; 0.743-0.833). The current study shows a statistically significant decrease in breast cancer incidence in association with previous Escherichia coli infection. Researching the relationship between single bacterial species is important as only up to 10% of breast cancer risk is attributable to genetics, while the contribution of environmental factors including previous infections potentially accounts for a majority of the preventable risk. Further evaluation is recommended to assess the potential and mechanism of E. coli in decreasing the risk of breast cancer.

Keywords: breast cancer, escherichia coli, incidence, infection, microbiome, risk

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