Search results for: metastatic testicular cancer

Authors: Laila Seada, Nouf Al Gharbi, Shaimaa Dawa

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Although skin cancers are prevalent worldwide, it is uncommon in Ha’il region in the Kingdom of Saudi Arabia, mostly non-melanoma sub-type. During a 4-year period from 2014 to 2017, out of a total of 120 cases of skin lesions, 29 non-melanoma cancers were retrieved from histopathology files obtained from King Khalid Hospital. As part of the study, all cases of skin cancer diagnosed during 2014 -2017 have been revised and the clinicopathological data recorded. The results show that Basal cell carcinoma (BCC) was the most common neoplasm (36%), followed by cutaneous lymphomas (mostly mycosis fungoides 25%), squamous cell carcinoma (SCC) (21%) and dermatofibrosarcoma protuberans (DFSP) (11%). Only one case of metastatic carcinoma was recorded. BCC nodular type was the most prevalent, with a mean age 57.6 years and mean size 2.73 cm. SCC was mostly grade 2, with mean size 1.9 cm and an older mean age of 72.3 cm. Increased size of lesion positively correlated with older age (p = 0.001). Non-melanoma skin cancer in Ha’il region is not frequently encountered. BCC is the most frequent followed by cutaneous T-cell lymphomas and SCC. The findings in this study were in accordance with other parts of, but much lower than other parts of the world.

Keywords: non melanoma skin cancer, Hail Region, histopathology, BCC

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Authors: Mahmoodreza Tahamtan

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Background: Malignant surface epithelial ovarian tumors (SEOT) account for approximately 90% of primary ovarian cancer. Wilms tumor gene (WT1) product was defined as a tumor suppressor gene, but today it is considered capable of performing oncogenic functions. There seems to be differences in WT1 expression patterns among SEOT subtypes. We evaluate the immunohistochemical expression of WT1 protein among different histologic subtypes of SEOT. Materials and Methods: Immunohistochemistry for WT1 was done on 35 serous cystadenocarcinomas, 9 borderline serous tumors, 3 mucinous cystadenocarcinomas, 10 borderline mucinous tumors, 7 endometrioid ovarian carcinomas, 3 clear cell carcinomas, 1 malignant Brenner tumor, 2 metastatic adenocarcinomas, and 6 endometrial adenocarcinomas. A tumor was considered negative if < 1% of tumor cells were stained.Positive reactions were graded as follows:1+,1%-24%; 2+,25%-49%; 3+,50%-74%; 4+,75%-100%. Results: Of the 35 cases of ovarian serous cystadenocarcinoma, 30(85.7%) were diffusely positive (3+,4+),4 showed reactivity of < 50% of the tumor cells (1+,2+), and one were negative. All 9 borderline serous tumors showed immunoreactivity with WT1. All the mucinous tumors(n:13), endometrioid carcinomas (n: 7), clear cell carcinomas (n: 3), metastatic adenocarcinomas (n: 2) and primary endometrial carcinomas (n:6) were negative. The single malignant Brenner tumor showed a positive reaction for WT1(4+) Conclusion: WT1 is a good marker to distinguish primary ovarian serous carcinomas from other surface epithelial tumors (especially endometrioid subtype) and metastatic carcinomas (especially endometrial serous carcinoma), other than malignant mesothelioma. We cannot rely to the degree of expression inorder to separate high grade borderline serous tumors from low grade ones.

Keywords: WT1, ovary, epithelial tumors, malignant

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Authors: Sadi-Guettaf Hassiba, Hadj-Bekkouche Fatima

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Dexamethasone (Dex) is a synthetic glucocorticoid that is used in therapy. However prolonged treatments with high doses are often required. This causes side effects that interfere with the activity of several endocrine systems, including the gonadotropic axis. The aim of our study is to determine the effect of Dex on testicular function in prepubertal Wistar rats. Newborn Wistar rats are submitted to intraperitoneal injection of Dex (1μg of Dex dissolved in NaCl 0.9% / 5g bw) for 20 days and then sacrificed at the age of 40days. A control group received NaCl 0.9%. The rat is weighed daily. The plasmatic levels of testosterone, LH and FSH were measured by radioimmunoassay. A histo-morphometric study was performed on sections of testis. Treated groups showed a significant decrease in body weight (p < 0.05), testis weight (p < 0.05) and plasma levels of testosterone (p < 0.05), of LH (P < .05) and FSH (p> 0.05). There is a reduction of seminiferous tubules average diameter and also of the seminiferous epithelium thickness with an increasing of lumen tubular. The diameter of the Leydig cells and Sertoli cell nucleus is also significantly reduced. Spermatogenesis is blocked at the stage round spermatid unlike witnesses or elongated spermatid stage is found. These results suggest that Dex administered during neonatal life influences testicular activity in the long term.

Keywords: dexamethasone, FSH, LH, rat, testis, testosterone

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Authors: Asma Zaib, Saeed Khan, Ayaz Ahmed Noonari, Sehrish Bint-e-Mohsin

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Breast cancer is the most common cancer among females worldwide and is estimated that more than 450,000 deaths are reported each year. It accounts for about 14% of all female cancer deaths. Angiogenesis plays an essential role in Breast cancer development, invasion, and metastasis. Breast cancer predominantly begins in luminal epithelial cells lining the normal breast ducts. Breast carcinoma likely requires coordinated efforts of both increased proliferation and increased motility to progress to metastatic stages.Resveratrol: a natural stilbenoid, has anti-inflammatory and anticancer effects that inhibits proliferation of variety of human cancer cell lines, including breast, prostate, stomach, colon, pancreatic, and thyroid cancers.The objective of this study is:To investigate anti-neoangiogenesis effects of Resveratrol in breast cancer and to analyze inhibitory effects of resveratrol on aromatase, Erα, HER2/neu, and VEGFR.Docking is the computational determination of binding affinity between molecule (protein structure and ligand).We performed molecular docking using Swiss-Dock and to determine docking effects of (1) Resveratrol with Aromatase, (2) Resveratrol with ERα (3) Resveratrol with HER2/neu and (4) Resveratrol with VEGFR2.Docking results of resveratrol determined inhibitory effects on aromatase with binding energy of -7.28 kcal/mol which shows anticancerous effects on estrogen dependent breast tumors. Resveratrol also show inhibitory effects on ERα and HER2/new with binging energy -8.02, and -6.74 respectively; which revealed anti-cytoproliferative effects upon breast cancer. On the other hand resveratrol v/s VEGFR showed potential inhibitory effects on neo-angiogenesis with binding energy -7.68 kcal/mol, angiogenesis is the important phenomenon that promote tumor development and metastasis. Resveratrol is an anti-breast cancer agent conformed by in silico studies, it has been identified that resveratrol can inhibit breast cancer cells proliferation by acting as competitive inhibitor of aromatase, ERα and HER2 neo, while neo-angiogemesis is restricted by binding to VEGFR which authenticates the anti-carcinogenic effects of resveratrol against breast cancer.

Keywords: angiogenesis, anti-cytoproliferative, molecular docking, resveratrol

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Authors: Yuping Liu, Li Tao, Yin Lu

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Accumulating evidence has been shown that diallyl trisulfide (DATS) from garlic may reduce the risk of developing several types of cancer. In view of the dynamic crosstalk interplayed by tumor cells and platelets in hematogenous metastasis, we demonstrate the effectiveness of DATS on the metastatic behaviors of MDA-MB-435s human breast cancer cell line co-incubated with activated platelets. Indeed, our data identified that DATS significantly blocked platelets fouction induced by PAF, followed by the decreased production of TXB2. DATS was found to dose-dependently suppressed MDA-MB-435s cell migration and invasion in presence of activated platelets by PAF in vitro. Furthermore, the expression, secretion and enzymatic activity of matrix metalloproteinase (MMP)-2/9, as well as the luciferase activity of upstream regulator NF-κB in MDA-MB-435s, were obviously diminished by DATS. In parallel, DATS blocked upstream NF-κB activation signaling complexes composed of extracellular signal-related kinase (ERK) as assessed by measuring the levels of the phosphorylated forms.

Keywords: DATS, ERK, metastasis, MMPs, NF-κB, platelet

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Authors: L. M. Al-Harbi, A. M. Shokry, J. S. M. Sabir, A. Chaudhary, J. Manikandan, K. S. Saini

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Breast cancer is the second most common cause of cancer death worldwide and is the most common malignancy among Saudi females. During breast carcinogenesis, a wide-array of cytogenetic changes involving deletions, or amplification, or translocations, of part or whole of chromosome regions have been observed. Because of the limitations of various earlier technologies, newer tools are developed to scan for changes at the genomic level. Recently, Array Comparative Genomic Hybridization (aCGH) technique has been applied for detecting segmental genomic alterations at molecular level. In this study, aCGH was performed on twenty breast cancer tumors and their matching non-tumor (normal) counterparts using the Agilent 2x400K. Several regions were identified to be either amplified or deleted in a tumor-specific manner. Most frequent alterations were amplification of chromosome 1q, chromosome 8q, 20q, and deletions at 16q were also detected. The amplification of genetic events at 1q and 8q were further validated using FISH analysis using probes targeting 1q25 and 8q (MYC gene). The copy number changes at these loci can potentially cause a significant change in the tumor behavior, as deletions in the E-Cadherin (CDH1)-tumor suppressor gene as well as amplification of the oncogenes-Aurora Kinase A. (AURKA) and MYC could make these tumors highly metastatic. This study validates the use of aCGH in Saudi breast cancer patients and sets the foundations necessary for performing larger cohort studies searching for ethnicity-specific biomarkers and gene copy number variations.

Keywords: breast cancer, molecular biology, ecology, environment

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Authors: Ghada E. Esheba, Ghufran Kheshaifaty, Kholoud Al-Harbi, Wafa'a Al-Harbi, Ala'a Al-Orabi, Moayad Turkistani

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Krukenberg tumor is a rare metastatic ovarian carcinoma that usually occurs in female between 30 - 40 year old and rarely seen after menopause. Stomach is the most common primary site. Histopathological features of krukenberg tumors appear as diffuse stromal proliferation, mucus-production, and numerous signet-cells and these tumors spread mostly by lymphatic route. Treatment and prognostic factors are not well established. This study describes a 34 year old female with a unilateral ovarian mass discovered accidentally during cesarean section delivery and it was misdiagnosed as luteoma of pregnancy, but histopathological examination showed a diffuse infiltration of the ovary and omentum by signet ring cells. These findings were not correlated with luteoma of pregnancy or any other types of primary ovarian tumors like surface epithelial tumor, sex cord stromal tumor or germ cell tumor. However, after the analysis of immunohistochemical results (negative CK7, positive CK20 and CDX-2), the finding was the diagnostic of metastatic krukenberg tumor. Two weeks later, the patient was evaluated and a large gastric tumor was found in her stomach and she underwent gastrectomy.

Keywords: CK7, CK20, CDX-2, Krukenburg tumor, metastatic ovarian tumor

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Authors: Ajay Gogia, Svs Deo, Dn Sharma, Atul Batra, Ashutash Mishra

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Background and Aims: Breast cancer in women aged less than 25 years (defined as very young breast cancer, VYBC) is rare and accounts for 0.25% of all breast cancer in the West. There is no data available on VYBC from developing countries. The aim of this study was to analyze the clinical, pathological, and prognostic factors and outcomes in VYBC. Methods: This retrospective analysis was performed on 80 patients aged 25 years or less (screened 8000 files of female BC) who were registered at All India Institute of Medical Sciences (AIIMS), New Delhi, India, over a 15-year period between 2011 and 2023. Results: The median age was 21.5 years (range 16-25). A positive family history (siblings and parents) was elicited in 30% of cases, and breast cancer gene (BRCA1/2) mutation was found in 33% of cases patients. Ten patients (12.5%) patients have pregnancy-associated breast cancer (BC detected during pregnancy or 1 year after postpartum period). The TNM stage distribution was Stage I was 0, stage II -30%, stage III –60% and Stage IV -10 %patients. Seventy percent of tumors were high grade, and 90% had pathological node-positive disease. Estrogen, Progesterone, and human epidermal growth factor receptor 2 (HER2)/neu positivity were 25%,25% and 35%, respectively. Triple-negative breast cancer constituted 40% of patients. With a median follow-up of 42 months, 3 years, relapse-free survival (nonmetastatic disease), progression-free survival (metastatic disease) and overall survival were 30%, 15% and 50%, respectively. Conclusions: Very young women constituted 1% of all breast cancer cases. Advanced disease at presentation and high-risk pathological features result in poor outcomes. One-third of VYBCs are associated with BRCA mutation, which requires genetic counseling and risk reduction surgery if required. Due to the aggressive behavior of BC in this age group, need early diagnosis and prompt treatment

Keywords: very young, breast cancer, outcome, developing country, India

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Authors: Sally Shepherd, Richard De Boer, Craig Murphy

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Background: Invasive lobular carcinoma (ILC) can metastasize to atypical sites within the peritoneal cavity, gastrointestinal, or genitourinary tract. Management varies depending on the symptom presentation, extent of disease burden, particularly if the primary disease is occult, and patient wishes. Case Series: 6 patients presented with general surgical presentations of ILC, including incomplete large bowel obstruction, cholecystitis, persistent lower abdominal pain, and faecal incontinence. 3 were diagnosed with their primary and metastatic disease in the same presentation, whilst 3 patients developed metastasis from 5 to 8 years post primary diagnosis of ILC. Management included resection of the metastasis (laparoscopic cholecystectomy), excision of the primary (mastectomy and axillary clearance), followed by a combination of aromatase inhibitors, biologic therapy, and chemotherapy. Survival post diagnosis of metastasis ranged from 3 weeks to 7 years. Conclusion: Metastatic ILC must be considered with any gastrointestinal or genitourinary symptoms in patients with a current or past history of ILC. Management may not be straightforward to chemotherapy if the acute pathology is resulting in a surgically resectable disease.

Keywords: breast cancer, gastrointestinal metastasis, invasive lobular carcinoma, metastasis

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Authors: Nitesh Kumar, Eoin Twohig, jasparl cheema, Sadiq mawji, Yousif al najjar

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Basal cell carcinoma (BCC) is the commonest cutaneous malignancy affecting humans. Despite this, distant spread is exceptionally rare. Metastatic BCC (mBCC) is estimated to occur in 0.0028 - 0.5%. it aim to illustrate with the aid of histological slides, a case of mBCC occurring in a fit and well 67-year-old. Initial diagnosis of desmoplastic BCC was made in 2006 from a scalp biopsy with the lesion then being excised. Re-excision of local recurrence was undertaken the following year. In 2014 the patient presented with an ipsilateral level 2a mass. Fine Needle Aspiration raised the suspicion of metastatic carcinoma. The patient had excision of two nodes from the left neck alongside pharyngeal tonsillectomy and tongue base biopsies. Histologically, the nodes closely resembled the immunophenotype of the initial scalp lesion. The patient subsequently had a modified radical neck dissection, and residual mBCC was excised from the left Sternocleidomastoid muscle. In 2023 the patient developed haematuria. On further investigation bilateral lung lesions on CT were noted with subsequent biopsy confirming mBCC. Spinal and renal lesions have also been found. Histopathology showed clear resemblance of the lung metastases to both those in the neck and the primary (scalp BCC) – with no squamous differentiation seen. The time span from primary to occurrence of lung metastasis (18 years) affirms the indolent and slow growing nature of BCC.  This case fulfils Lattes and Kessler diagnostic criteria. High risk cases are described as those with advanced local presentation, primary tumour on the Head and Neck and locally recurrent lesions.

Keywords: BCC, metastasis, rare, skin cancer

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Authors: Maryam Parsian, Pelin Mutlu, Ufuk Gunduz

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Two-dimensional cell culture affords simplicity and low cost, but it has serious limitations; lacking cell-cell and cell-matrix interactions that are present in tissues. Cancer cells grown in 3D culture systems have distinct phenotypes of adhesion, growth, migration, invasion as well as profiles of gene and protein expression. These interactions cause the 3D-cultured cells to acquire morphological and cellular characteristics relevant to in vivo tumors. Palbociclib is a chemotherapeutic agent for the treatment of ER-positive and HER-negative metastatic breast cancer. Poly-amidoamine (PAMAM) dendrimer is a well-defined, special three-dimensional structure and has a multivalent surface and internal cavities that can play an essential role in drug delivery systems. In this study, palbociclib is loaded onto the magnetic PAMAM dendrimer. Hanging droplet method was used in order to form 3D spheroids. The possible toxic effects of both free drug and drug loaded nanoparticles were evaluated in 2D and 3D MCF-7, MD-MB-231 and SKBR-3 breast cancer cell culture models by performing MTT cell viability and Alamar Blue assays. MTT analysis was performed with six different doses from 1000 µg/ml to 25 µg/ml. Drug unloaded PAMAM dendrimer did not demonstrate significant toxicity on all breast cancer cell lines. The results showed that 3D spheroids are clearly less sensitive than 2D cell cultures to free palbociclib. Also, palbociclib loaded PAMAM dendrimers showed more toxic effect than free palbociclib in all cell lines at 2D and 3D cultures. The results suggest that the traditional cell culture method (2D) is insufficient for mimicking the actual tumor tissue. The response of the cancer cells to anticancer drugs is different in the 2D and 3D culture conditions. This study showed that breast cancer cells are more resistant to free palbociclib in 3D cultures than in 2D cultures. However, nanoparticle loaded drugs can be more cytotoxic when compared to free drug.

Keywords: 2D and 3D cell culture, breast cancer, palbociclibe, PAMAM magnetic nanoparticles

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Authors: Ahmad Shanei, Milad Baradaran-Ghahfarokhi

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This study aimed to investigate testicular dose (TD) and the associated risk of heritable disease from common pelvis radiotherapy of male patients in Iran. In this work, the relation between TD and changes in beam energy, pelvis size, source to skin distance (SSD) and beam directions (anterior or posterior) were also evaluated. The values of TDs were measured on 67 randomly selected male patients during common pelvis radiotherapy using 1.17 and 1.33 MeV, Theratron Cobalt-60 unit at SSD of 80 cm and 9 MV, Neptun 10 PC and 18 MV, GE Saturne 20 at SSD of 100 cm at Seyed-Al Shohada Hospital, Isfahan, Iran. Results showed that the maximum TD was up to 12% of the tumor dose. Considering the risk factor for radiation-induced heritable disorders of 0.1% per Sv, an excess risk of hereditary disorders of 72 per 10000 births was conservatively calculated. There was a significant difference in the measured TD using different treatment machines and energies (P < 0.001). The TD at 100 cm SSD were much less than that for 80 cm SSD (P <0.001). The Pearson Correlation test showed that, as expected, there was a strong correlation between TD and patient’s pelvis size (r = 0.275, P <0.001). Using the student’s t-tests, it was found that, there was not a significant difference between TD and beam direction (P = 0.231). Iranian male patients undergoing pelvic radiotherapy have the potential of receiving a TD of more than 1 Gy which might result in temporary azoospermia. The risk for induction of hereditary disorders in future generations should be considered as low but not negligible in comparison with the correspondent nominal risk.

Keywords: pelvis radiotherapy, testicular dose, infertility, hereditary effects

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Authors: Angelis P. Barlampas

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Introduction: The term phantom lung mass describes the ovoid collection of fluid within the interlobular fissure, which initially creates the impression of a mass. The problem of correct differential diagnosis is great, especially in plain radiography. A case is presented with three nodular pulmonary foci, the shape, location, and density of which, as well as the presence of chronic loculated pleural effusions, suggest the presence of multiple phantom tumors of the lung. Purpose: The aim of this paper is to draw the attention of non-experienced and non-specialized physicians to the existence of benign findings that mimic pathological conditions and vice versa. The careful study of a radiological examination and the comparison with previous exams or further control protect against quick wrong conclusions. Methods: A hospitalized patient underwent a non-contrast CT scan of the chest as part of the general control of her situation. Results: Computed tomography revealed pleural effusions, some of them loculated, increased cardiothoracic index, as well as the presence of three nodular foci, one in the left lung and two in the right with a maximum density of up to 18 Hounsfield units and a mean diameter of approximately five centimeters. Two of them are located in the characteristical anatomical position of the major interlobular fissure. The third one is located in the area of the right lower lobe’s posterior basal part, and it presents the same characteristics as the previous ones and is likely to be a loculated fluid collection, within an auxiliary interlobular fissure or a cyst, in the context of the patient's more general pleural entrapments and loculations. The differential diagnosis of nodular foci based on their imaging characteristics includes the following: a) rare metastatic foci with low density (liposarcoma, mucous tumors of the digestive or genital system, necrotic metastatic foci, metastatic renal cancer, etc.), b) necrotic multiple primary lung tumor locations (squamous epithelial cancer, etc. ), c) hamartomas of the lung, d) fibrotic tumors of the interlobular fissures, e) lipoid pneumonia, f) fluid concentrations within the interlobular fissures, g) lipoma of the lung, h) myelolipomas of the lung. Conclusions: The collection of fluid within the interlobular fissure of the lung can give the false impression of a lung mass, particularly on plain chest radiography. In the case of computed tomography, the ability to measure the density of a lesion, combined with the provided high anatomical details of the location and characteristics of the lesion, can lead relatively easily to the correct diagnosis. In cases of doubt or image artifacts, comparison with previous or subsequent examinations can resolve any disagreements, while in rare cases, intravenous contrast may be necessary.

Keywords: phantom mass, chest CT, pleural effusion, cancer

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Authors: Mohammad Alfaifi

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Organophosphates are among the most widely used synthetic insect pesticides. The widespread use of organophosphates has stimulated research into the possible existence of effects related with their reproductive toxic activity. The present study aimed to assess the effects of diazinon (DIZ) on male reproductive system. DIZ at the dose levels of 1.5, 3.0 and 9.0 mg/kg b. wt./day was administered orally to male rats of Wistar strain for 30 days to evaluate the toxic alterations in testicular histology, biochemistry, sperm dynamics, and testosterone levels. The body weight of animals did not show any significant changes, however, a significant reduction was observed in testes weight. DIZ also brought about marked reduction in epididymal and testicular sperm counts in exposed males and a decrease in serum testosterone concentration. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. Fertility test showed 79% negative results. All these toxic effects are moderate at low doses and become severe at higher dose levels. From the results of the present study it is concluded that DIZ induces severe testicular damage and results in reduction in sperm count and thus affect fertility. Small changes in sperm counts are known to have adverse affects on human fertility. Therefore, application of such insecticide should be limited to a designed programme.

Keywords: reproductive toxicity, fertility, diazinon, sperm count

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Authors: Mohammad Alfaifi, Mohammed Alshehri

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Organophosphates are among the most widely used synthetic insect pesticides. The widespread use of organophosphates has stimulated research into the possible existence of effects related with their reproductive toxic activity. The present study aimed to assess the effects of diazinon (DIZ) on male reproductive system. DIZ at the dose levels of 1.5, 3.0 and 9.0 mg/kg b. wt./day was administered orally to male rats of Wistar strain for 30 days to evaluate the toxic alterations in testicular histology, biochemistry, sperm dynamics and testosterone levels. The body weight of animals did not show any significant changes; however, a significant reduction was observed in testes weight. DIZ also brought about a marked reduction in epididymal and testicular sperm counts in exposed males and a decrease in serum testosterone concentration. Histopathological examination of testes showed mild to severe degenerative changes in seminiferous tubules at various dose levels. Fertility test showed 79% negative results. All these toxic effects are moderate at low doses and become severe at higher dose levels. From the results of the present study, it is concluded that DIZ induces severe testicular damage and results in a reduction in sperm count and thus affect fertility. Small changes in sperm counts are known to have adverse effects on human fertility. Therefore, application of such insecticide should be limited to a designed programme.

Keywords: organophosphates, reproductive toxicity, diazinon, fertility

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Authors: Joseph M. Rich, Vinay A. Duddalwar, Assad A. Oberai

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Prostate adenocarcinoma is the most common cancer in males, with osseous metastases as the commonest site of metastatic prostate carcinoma (mPC). Treatment monitoring is based on the evaluation and characterization of lesions on multiple imaging studies, including Computed Tomography (CT). Monitoring of the osseous disease burden, including follow-up of lesions and identification and characterization of new lesions, is a laborious task for radiologists. Deep learning algorithms are increasingly used to perform tasks such as identification and segmentation for osseous metastatic disease and provide accurate information regarding metastatic burden. Here, nnUNet was used to produce a model which can segment CT scan images of prostate adenocarcinoma vertebral bone metastatic lesions. nnUNet is an open-source Python package that adds optimizations to deep learning-based UNet architecture but has not been extensively combined with transfer learning techniques due to the absence of a readily available functionality of this method. The IRB-approved study data set includes imaging studies from patients with mPC who were enrolled in clinical trials at the University of Southern California (USC) Health Science Campus and Los Angeles County (LAC)/USC medical center. Manual segmentation of metastatic lesions was completed by an expert radiologist Dr. Vinay Duddalwar (20+ years in radiology and oncologic imaging), to serve as ground truths for the automated segmentation. Despite nnUNet’s success on some medical segmentation tasks, it only produced an average Dice Similarity Coefficient (DSC) of 0.31 on the USC dataset. DSC results fell in a bimodal distribution, with most scores falling either over 0.66 (reasonably accurate) or at 0 (no lesion detected). Applying more aggressive data augmentation techniques dropped the DSC to 0.15, and reducing the number of epochs reduced the DSC to below 0.1. Datasets have been identified for transfer learning, which involve balancing between size and similarity of the dataset. Identified datasets include the Pancreas data from the Medical Segmentation Decathlon, Pelvic Reference Data, and CT volumes with multiple organ segmentations (CT-ORG). Some of the challenges of producing an accurate model from the USC dataset include small dataset size (115 images), 2D data (as nnUNet generally performs better on 3D data), and the limited amount of public data capturing annotated CT images of bone lesions. Optimizations and improvements will be made by applying transfer learning and generative methods, including incorporating generative adversarial networks and diffusion models in order to augment the dataset. Performance with different libraries, including MONAI and custom architectures with Pytorch, will be compared. In the future, molecular correlations will be tracked with radiologic features for the purpose of multimodal composite biomarker identification. Once validated, these models will be incorporated into evaluation workflows to optimize radiologist evaluation. Our work demonstrates the challenges of applying automated image segmentation to small medical datasets and lays a foundation for techniques to improve performance. As machine learning models become increasingly incorporated into the workflow of radiologists, these findings will help improve the speed and accuracy of vertebral metastatic lesions detection.

Keywords: deep learning, image segmentation, medicine, nnUNet, prostate carcinoma, radiomics

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Authors: Magdalena Korytowska, Gunnar Lengstrand, Cecilia Larsson Wexell

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Background: Breast cancer (BC) is the most common cancer among women worldwide, and cases are continuing to increase in Sweden. Bone is the most common metastatic site in breast cancer patients, where > 65-75% of women with advanced breast cancer develop bone metastases during their disease. To prevent the skeletal-related events of metastases (e.g., pathological fractures, bone loss, cancer-induced bone pain, and hypercalcemia bone), two different classes of antiresorptive medications (AR), bisphosphonate and denosumab are typically administered every 3 to 4 weeks. Since 2015, adjuvant bisphosphonate treatment has been used every six months for three to five years in postmenopausal women for the prevention of skeletal metastases and improved survival. Methods: A case-control study was conducted to test the hypotheses that patients treated with high-dose AR are at higher risk of developing MRONJ than breast cancer patients with adjuvant bisphosphonate treatment at a lower dose. Medical and odontological data was collected between 2015-2020. Assessment of oral health and dental care before and during oncological treatment took place at the specialist clinic for Orofacial medicine linked to the specific hospital. Results: In total, 220 patients were included, 101 patients in the high-dose group and 119 patients in the adjuvant BP-treatment group. MRONJ was diagnosed in 13 patients (14%) in the high-dose group. The mandible was affected in most of the cases (84.6%), with a mean duration of high-dose treatment of 19.7 months. In 46.2% of cases, no dental cause of MRONJ could be identified. Overall, estrogen receptor-positive (ER+) BC was the most representative type in 172 patients (78.2%). However, this was 83.9% in the high-dose cases group. The most used drug was denosumab. Twenty-five patients (26.9%) switched their medication from ZOL to denosumab during their oncological treatment. Patients with ER+ breast cancer were reported in 88 patients (87.8%) in the adjuvant group that was treated with ZOL. Conclusions: MRONJ was diagnosed only in the high-dose AR group. Dental assessment and care of patients in the adjuvant group should be considered, with a recommendation to potentially prolong ZOL treatment from 3 to 5 years, with concomitant use of hormonal therapy in patients diagnosed with ER+ breast cancer to prevent bone loss induced by oncological treatment. A new referral for dental assessment is very important in the case of bone metastases when treatment with high dose AR will be required since it is associated with a higher risk of MRONJ.

Keywords: antiresorptive therapy, breast cancer, dental care, MRONJ

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

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Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

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Authors: Sonal Sethi, Mukesh Yadav, Abhimanyu Gupta

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The upcoming field of radiogenomics has the potential to upgrade the role of imaging in lung cancer management by noninvasive characterization of tumor histology and genetic microenvironment. Receptor positivity like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genotyping are critical in lung adenocarcinoma for treatment. As conventional identification of receptor positivity is an invasive procedure, we analyzed the features on non-invasive computed tomography (CT), which predicts the receptor positivity in lung adenocarcinoma. Retrospectively, we did a comprehensive study from 77 proven lung adenocarcinoma patients with CT images, EGFR and ALK receptor genotyping, and clinical information. Total 22/77 patients were receptor-positive (15 had only EGFR mutation, 6 had ALK mutation, and 1 had both EGFR and ALK mutation). Various morphological characteristics and metastatic distribution on CT were analyzed along with the clinical information. Univariate and multivariable logistic regression analyses were used. On multivariable logistic regression analysis, we found spiculated margin, lymphangitic spread, air bronchogram, pleural effusion, and distant metastasis had a significant predictive value for receptor mutation status. On univariate analysis, air bronchogram and pleural effusion had significant individual predictive value. Conclusions: Receptor positive lung cancer has characteristic imaging features compared with nonreceptor positive lung adenocarcinoma. Since CT is routinely used in lung cancer diagnosis, we can predict the receptor positivity by a noninvasive technique and would follow a more aggressive algorithm for evaluation of distant metastases as well as for the treatment.

Keywords: lung cancer, multidisciplinary cancer care, oncologic imaging, radiobiology

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Authors: Ramin Mehdiabadi, Neda Menbari, Mohammad Nazir Menbari

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As a pressing public health concern, breast cancer stands as the predominant oncological diagnosis and principal cause of cancer-related mortality among women globally, accounting for 11.7% of new cancer incidences and 6.9% of cancer-related deaths. The annual figures indicate that approximately 230,480 women are diagnosed with breast cancer in the United States alone, with 39,520 succumbing to the disease. While developed economies have reported a deceleration in both incidence and mortality rates across various forms of cancer, including breast cancer, emerging and low-income economies manifest a contrary escalation, largely attributable to lifestyle-mediated risk factors such as tobacco usage, physical inactivity, and high caloric intake. Breast cancer is distinctly characterized by molecular heterogeneity, manifesting in specific subtypes delineated by biomarkers—Estrogen Receptors (ER), Progesterone Receptors (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These subtypes, comprising Luminal A, Luminal B, HER2-enriched, triple-negative/basal-like, and normal-like, necessitate nuanced, subtype-specific therapeutic regimens, thereby challenging the applicability of generalized treatment protocols. Within this molecular complexity, the transcription factor Forkhead Box M1 (FoxM1) has garnered attention as a significant driver of cellular proliferation, tumorigenesis, metastatic progression, and treatment resistance in a spectrum of human malignancies, including breast cancer. Concurrently, microRNAs (miRs), specifically miR-216b-5p, have been identified as post-transcriptional gene expression regulators and potential tumor suppressors. The overarching objective of this academic investigation is to explicate the multifaceted interrelationship between FoxM1 and miR-216b-5p across the disparate molecular subtypes of breast cancer. Employing a methodologically rigorous, interdisciplinary research design that incorporates cutting-edge molecular biology techniques, sophisticated bioinformatics analytics, and exhaustive meta-analyses of extant clinical data, this scholarly endeavor aims to unveil novel biomarker-specific therapeutic pathways. By doing so, this research is positioned to make a seminal contribution to the advancement of personalized, efficacious, and minimally toxic treatment paradigms, thus profoundly impacting the global efforts to ameliorate the burden of breast cancer.

Keywords: breast cancer, fox m1, microRNAs, mir-216b-5p, gene expression

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Authors: Shirui Huang, Wei Chen, Chuanshu Huang

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Basal muscle-invasive bladder cancer (BMIBC) is considered one of the subtypes of BC with the highest metastatic rate and the poorest prognosis. Therefore, elucidating the mechanisms underlying BMIBC metastasis and identifying novel precision therapeutic targets are current research hotspots and challenges to cancer researchers. Through a series of in vitro and in vivo functional experiments, we have identified the crucial role of KRT14 in the high invasiveness and adverse prognosis of BMIBC. We found that the K294 site within the IGF2BP1-KH2 domain is responsible for reading the conserved genetic information carried by D226/E227 in the KRT14 nuclear export signal (NES). Activation of the KRT14-IGF2BP1 signaling axis is essential for IGF2BP1-mediated stabilization of SNAI1 mRNA through FTO modification. Additionally, IGF2BP1 forms a positive feedback loop by stabilizing its own mRNA, thereby accelerating the invasion and metastasis of BMIBC. Collectively, our study identifies the KRT14/IGF2BP1/FTO/Snail signaling axis as an essential regulatory mechanism associated with poor prognosis in BMIBC, providing a theoretical basis for KRT14 and its downstream regulated molecules as therapeutic targets for BMIBC and the development of corresponding targeted therapies.

Keywords: BMIBC, KRT4, IFGF2BP1, DNA methylation

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Authors: Hyekyung Woo, Gwihyun Kim

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mHealth, which encompasses mobile health technologies and interventions, is rapidly evolving in various medical specialties, and its impact is evident in oncology. This review describes current trends in research addressing the integration of mHealth into the management of breast cancer by examining evaluations of mHealth and its contributions across the cancer care continuum. Mobile technologies are perceived as effective in prevention and as feasible for managing breast cancer, but the diagnostic accuracy of these tools remains in doubt. Not all phases of breast cancer treatment involve mHealth, and not all have been addressed by research. These drawbacks in the application of mHealth to breast cancer management call for intensified research to strengthen its role in breast cancer care.

Keywords: mobile application, breast cancer, content analysis, mHealth

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Authors: Leila Rashki Ghaleno, Mohamad Amin Hajari, Leila Montazeri, Abdolhossein Shahverdi, Mojtaba Rezazadeh Valojerdi

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Background: Spermatogonia stem cells (SSCs) exhibit pluripotency, enabling them to undergo differentiation into many cell lineages, including neurons, glia, endothelial cells, and hepatocytes when cultured in vitro. Although the specific mechanisms are not yet fully understood, it has been observed that biopolymer agents, such as hyaluronic acid (HA) and alginate (Alg), have the potential to induce transdifferentiation of SSCs. The current work aimed to examine the process of in vitro spermatogenesis and the conversion of mouse testicular cells into hepatocytes and erythrocyte-like cells utilizing the HA-Alg hydrogel. Method: After being extracted from the testes of a 5-day postpartum mouse (5 DPP), the testicular cells were separated into two enzymatic stages and then put into a composite hydrogel containing 0.5% HA and 1% alginate. On days 14 and 28 of culture, the colonies' growth, the cells' viability, and their histology were assessed. Result: Despite observing significant cell proliferation on day 14 and the development of circular-shaped organoids on day 28, it was noted that the organoids generated in the HA-Alg medium tended to maintain their circular morphology on day 28. Notably, the testicular cells underwent transdifferentiation into cell types resembling erythrocytes and hepatocytes. The hepatocyte-like cells exhibited the presence of glycogen and lipid deposits, indicating their hepatocyte-like characteristics. Interestingly, immunostaining analysis revealed the secretion of albumin and the presence of VEGFR on day 14. However, on day 28, albumin expression was not detected, while the expression of Sox9 (a marker for hepatocytes), Vegf, CD34, and C-kit (markers for erythrocytes) showed increased levels in the gene expression evaluation. Conclusion: The present findings indicated that HA-Alg could be a potent and effective agent for the transdifferentiation of testis cells into erythrocyte and hepatocyte-like cells, as recent studies have confirmed the transformation of SSCs into hepatocyte cells during in vitro culture.

Keywords: 3D culture, mouse testicular cell, hyaluronic acid, liver organoids

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Authors: Saleh N. Maodaa

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Background: Lead (Pb) is an environmental pollutant causing serious health problems, including impairment of reproduction. Visnagin (VIS) is a furanochromone with promising antioxidant and anti-inflammatory effects; however, its protective efficacy against Pb toxicity has not been investigated. Objective: This study evaluated the protective effect of VIS on Pb reproductive toxicity, impaired steroidogenesis and spermatogenesis, oxidative stress and inflammation. Methods: Rats received VIS (30 or 60 mg/kg) and 50 mg/kg lead acetate for 3 weeks, and blood and testes samples were collected. Results: Pb intoxication impaired the pituitary-testicular axis (PTA), manifested by the decreased serum levels of gonadotropins and testosterone. Pb decreased sperm count, motility and viability, increased sperm abnormalities, and downregulated the steroidogenesis markers StAR, CYP17A1, 3β-HSD and 17β-HSD in the testis of rats. VIS significantly increased serum gonadotropins and testosterone, alleviated sperm parameters and upregulated steroidogenesis. In addition, VIS decreased pro-inflammatory cytokines, testicular lipid peroxidation and DNA fragmentation, downregulated Bax, and enhanced antioxidants and Bcl-2 Conclusion: These results demonstrate the protective effect of VIS against Pb reproductive toxicity in rats. VIS improved serum gonadotropins and testosterone, enhanced steroidogenesis and spermatogenesis, and attenuated oxidative injury, inflammation and apoptosis. Therefore, VIS is a promising candidate for the protection against Pb-induced reproduction impairment.

Keywords: pituitary-gonadal axis, cytokines, DNA damage, apoptosis

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Authors: Fakhrosadat Sajjadian

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The majority of deaths in cancer patients are caused by distant metastasis. Breast cancer shows a unique spread pattern, often affecting bone, liver, lung, and brain. Breast cancer can be categorized into various subtypes according to gene expression patterns, and these subtypes exhibit specific preferences for organs where metastasis occurs. Breast tumors with luminal characteristics have a preference for spreading to the bone, whereas basal-like breast cancer (BLBC) shows a tendency to metastasize to the lungs. Still, the mechanisms behind this particular pattern of metastasis in organs have yet to be fully understood. In this evaluation, we will outline the latest progress in molecular signaling pathways and treatment methods for breast cancer lung metastasis.

Keywords: lung cancer, liver cancer, diagnosis, BLBC, metastasis

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: children, C-reactive protein, systemic immune-inflammation index, obesity

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Authors: Amir Ghasemlouei, Alireza Khalaj

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In women, cancer of the breast is one of the most common incident cancer and cause of death from cancer .we reviewed the prevalence of obesity and its association with breast cancer. In this study, a total of 25 articles regarding the subject matter of the article have been presented in which 640 patients were examined that 320 patients with breast cancer and 320 were controls. The distribution of breast cancer patients and controls with respect to their anthropometric indices in patients with higher weight, which was statistically significant (60.2 ± 10.2 kg) compared with control group (56.1 ± 11.3 kg). The body mass index of patients was (26.06+/-3.42) and significantly higher than the control group (24.1+/-1.7). Obesity leads to increased levels of adipose tissue in the body that can be stored toxins and carcinogens to produce a continuous supply. Due to the high level of fat and the role of estrogen in a woman is endogenous estrogen of the tumor and regulate the activities of growth steroids, obesity is a risk factor for breast cancer is confirmed. Our study and other studies show that obesity is a risk factor for breast cancer. And with a weight loss intervention for breast cancer can be prevented in the future.

Keywords: breast cancer, review study, obesity, overweight

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Authors: Sachinkumar Patil, Sonali Patil, Shitalkumar Patil

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Nanoparticles played important role in the biomedicine. New advanced methods having great potential apllication in the diagnosis and therapy of cancer. Now a day’s magnetic nanoparticles used in cancer therapy. Cancer is the major disease causes death. Magnetic nanoparticles show response to the magnetic field on the basis of this property they are used in cancer therapy. Cancer treated with hyperthermia by using magnetic nanoparticles it is unconventional but more safe and effective method. Magnetic nanoparticles prepared by using different innovative techniques that makes particles in uniform size and desired effect. Magnetic nanoparticles already used as contrast media in magnetic resonance imaging. A magnetic nanoparticle has been great potential application in cancer diagnosis and treatment as well as in gene therapy. In this review we will discuss the progress in cancer therapy based on magnetic nanoparticles, mainly including magnetic hyperthermia, synthesis and characterization of magnetic nanoparticles, mechanism of magnetic nanoparticles and application of magnetic nanoparticles.

Keywords: magnetic nanoparticles, synthesis, characterization, cancer therapy, hyperthermia, application

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Authors: Ramandeep Kaur, Gurjit Singh Bhathal

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Cancer diagnosis is very difficult task. Magnetic resonance imaging (MRI) scan is used to produce image of any part of the body and provides an efficient way for diagnosis of cancer or tumor. In existing method, fuzzy clustering mean (FCM) is used for the diagnosis of the tumor. In the proposed method FCM is used to diagnose the cancer of the foot. FCM finds the centroids of the clusters of the foot cancer obtained from MRI images. FCM thresholding result shows the extract region of the cancer. Morphological operations are applied to get extracted region of cancer.

Keywords: magnetic resonance imaging (MRI), fuzzy C mean clustering, segmentation, morphological operations

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Authors: Nesreen M. Alqaissi

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Little is known about the lived experiences of breast cancer among Arab Muslim women. The researcher used a qualitative interpretive phenomenological research design to explore the lived experiences of breast cancer as described by Jordanian Muslim women. A purposive sample of 20 women with breast cancer was recruited. Data were collected utilizing individual semi-structured interviews, and analyzed using Heideggerian Hermeneutical methodology. Results: Five related themes and one constitutive pattern: (a) breast cancer means death; (b) matriarchal family members as important source of support; (c) spirituality as a way to live and survive breast cancer; (d) concealing cancer experiences to protect self and families; (e) physicians as protectors and treatment decision makers; (f) the constitutive pattern: culture influencing Jordanian women experiences with breast cancer. In conclusion, researchers and healthcare providers should consider the influence of culture, spirituality, and families, when caring for women with breast cancer from Jordan.

Keywords: breast cancer, Arab Muslim, Jordan, lived experiences, spirituality, culture

Procedia PDF Downloads 515