Radiation-associated cardiac disease frequently affects cancer patients when radiation fields overlap the heart, but relationships between cardiac substructure dose and specific cardiac events remain poorly understood. This study examined associations between radiation dose to cardiac substructures and adverse cardiac events in thoracic malignancy patients. We retrospectively analyzed 94 patients with lung, esophageal and breast cancers who received radiation therapy. Radiation-induced adverse cardiac events included pericardial disease, atrial fibrillation/flutter, heart failure and valve disease. We evaluated associations between cardiac substructure radiation doses and adverse event types. Results showed that increasing radiation doses to the pericardium, left atrium and whole heart were associated with higher odds of pericardial disease. Median onset times varied: 7 months for pericardial disease, 10 months for atrial fibrillation/flutter and 16 months for heart failure. Clear associations emerged between specific cardiac substructure radiation doses and corresponding adverse event types. Sex-specific differences in cardiac substructure radiation dose were also identified. These findings demonstrate important relationships between cardiac substructure radiation exposure and specific adverse events in patients receiving thoracic radiation therapy. The results underscore the critical importance of considering both cardiac substructure dose distributions and patient sex when developing strategies to mitigate treatment-related cardiac risks in cancer patients.
Background: Breast cancer is one among the foremost common malignancies in women worldwide, and one among the leading causes of cancer-related death. The decimal prognosis of breast cancer subtypes including triple negative breast cancer has been linked with immune response. So our aim to evaluate the programmed death and tumor infiltrating lymphocytes in prognosis of breast cancer subtypes including triple negative breast cancer subtypes. Methods: Systematic review for evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Breast Cancer. The outcomes evaluated are going to be Overall Survival, Breast Cancer-specific Survival, Disease-free Survival, Recurrence-free Survival, Positive lymph gland, and Distant Metastasis. Discussion: Immunomodulation seems to be a promising strategy in solid tumors. Worldwide, breast cancer is the most common malignancies in women, and one of the leading causes of cancer death. PD-1 and PD-L1 are key physiologic suppressors of the cytotoxic immune response.
Cervical cancer is the second commonest cancer in India. Early detection of cervical cancer has significant improvement on patient survival, morbidity and also decreases economic burden on treatment cost. Screening for cervical cancer with conventional Pap smear (CPS) is still widely used investigation in low resource settings like India. In this study we are presenting CPS which includes non-neoplastic and neoplastic conditions. The non-neoplastic conditions like Candida, Bacterial vaginosis, Trichomoniasis, koilocytic atypia and malignancy are correlated with histopathology and p16 Immunohistochemical (IHC) marker where ever possible. The non-neoplastic inflammatory conditions cause disruption of the cervical microflora and discontinuity of cervical epithelium. This leads to increased susceptibility for oncogenic HPV. When HPV enters cervical epithelium, it remains dormant for prolonged period. As it enters replication, the E6, E7 genes cause inhibition of p53 and RB tumor suppressor genes respectively. This negative feedback of RB gene by E7 leads to increased expression of p16 (CDK inhibitor) in infected cells. The increased p16 immunoreactivity in epithelium shows HPV infectivity, such lesions have greater tendency to upgrade itself to carcinoma. Our study tries to substantiate the above principle of HPV infection leading to cancer with non-neoplastic conditions being cofactors. CPS is a good screening technique even with its limitations like obscuring factors which can be overcome by biopsy and p16 marker study. Thus, women in developing countries can be protected from precancerous and cancerous conditions of cervix by easy method like CPS.
Breast cancer is the 2nd most common cancer in urban Indian population because of changes in lifestyle, better economic status. Thus it is imperative to diagnose, treat and increase the survival of these women especially in low to middle income group countries like India. There are several biomarkers available which are important and play a role in diagnosis, treatment and prognosis of breast lesions. Steroid markers like estrogen (ER) and progesterone (PR) are nuclear markers which are important for treatment and prognosis. Overexpression of HER2/neu a cell membrane marker and Ki67 a proliferation marker are important for treatment and prognosis. Metastatic markers like E-cadherin and vimentin which when decreased are associated with increased chances of metastasis. It is also related to increased ER expression and tumor budding (TB). Other factors like increase in angiogenesis leads to bad prognosis which can be identified by markers like CD34 and vascular endothelial growth factor (VEGF). All the above markers can be studied by various methods like Fine Needle Aspiration Cytology (FNAC), Manual Liquid Based Cytology (MLBC), Cell Block (CB) and histopatholgy sections. Each method have their advantages and limitations which will be highlighted in the study.
Cervical cancer is the second commonest cancer in India. Early detection of cervical cancer has significant improvement on patient survival, morbidity and decreases economic burden on treatment cost. Invasive cancer of the cervix has been considered preventable because it has a long pre-invasive state, cervical cytology screening programmes are available and the treatment of pre-invasive lesions is effective. Cervical screening programmes aims to detect women who have an epithelial abnormality. Screening for cervical cancer with conventional Pap smear (CPS) is still widely used investigation in low resource settings like India. It has been the mainstay for screening which has led to substantial reduction in cancer incidence. The Bethesda System of Reporting Cervical Cytology- 2014 (TBS) has been widely accepted and used as it brings uniformity for reporting. CPS are required not only for the diagnosis and management of the malignant lesions but it is also helpful in identifying the infectious etiologies and treatment in developing countries. Aims of TBS were to provide effective communication from the laboratory to the clinical provider; facilitate cytologic-histologic correlation; facilitate research into the epidemiology, pathology of cervical disease; and provide reproducible and reliable data for national and international statistical analysis comparisons. Our study aims at categorization of cervical lesions according to TBS in a low to mid income country (LMIC) like India and to eliminate the diagnostic dilemma.
Breast cancer is the most common cancer in urban Indian women with age adjusted rate of 25.8 and mortality of 12.7 per 1,00,000 women. Prognosis is greatly determined by clinicopathological and molecular characteristics of the tumor. Hormone receptor status evaluation has become a critical determinant for classification and management of breast cancer. Estrogen receptor (ER) status has emerged as important criteria in determining the prognosis and treatment as it plays a major role in tumor metastasis. Aim of this study is to assess the relationship between morphological features and hormone receptor status of invasive breast carcinoma. This is a retrospective study of 25 cases of breast carcinoma diagnosed between July2020-December2020 in the department of pathology, JSS Medical college, Mysore. The tumors were categorized into ER+PR+ (36%), ER+PR-(20%), ER-PR+ (0%), ER-PR-(44%). Well differentiated low grade invasive carcinomas were frequently ER+PR+ whereas high grade infiltrating carcinomas were mainly ER-PR-. Tumor necrosis, lymphovascular invasion, lymph node involvement, high tumor grade were more frequently associated with ER-PR- status. Histopathological evaluation and grading of breast cancer substantiated by hormone receptor status forms a reliable tool in determining treatment modality and prognosis of the patient.
The pandemic of COVID-19 has been plaguing the world. The social distance and uncertainty about the future, brought changes in our life habits. As a consequence, the level of anxiety seems to have increased during this period. The level of anxiety experienced by cancer patients may differ from an individual healthy. Therefore, the main goal of this research was verify if the cancer patients are spending the minutes for week of physical activity (PAm) recommended by World Health Organization (WHO), and correlate it with the anxiety level of them. An online questionnaire was applied among cancer patients, being evaluated 57 women diagnosed with breast cancer (BC), aged between 20 and 75 years. The questionnaire was sent by text message and in spontaneous demand on social networks. As main results we observed that before pandemic 87.7% were exercising regularly, while only 70.2% of them could maintain this habit. Regarding the amount of minutes spent for week with physical activity, we found a mean of 90.5 vs 69.4 minutes before and during pandemic respectively. Considering the minimum of WHO’s recomendation to PAm (150-300 of moderate or 75-150 of vigorous PA) we found that, comparing before and during pandemic, 24.5% vs 14% of BC patients reached the necessary amount of minutes. Finally, the level of anxiety was negatively correlated with amount PAm. Therefore, regarding BC patients, we conclude that during the pandemic of COVID-19: 1. the engaging with PA was reduced by 17.5%; 2. the amount of PAm was reduced by 23.3%; 3. the minimum of WHO’s recomendation to PAm was not reached, neither before nor during the pandemic; 4. increase the PAm seems to be useful, not medicated, option against anxiety.
Heavy infection of the virus leads to overproduction of cytokines. The overproduction of cytokine (cytokines storms) is responsible for the critical cases and deaths of COVID-19. The nuclear factor kappa-B stimulates the expression of the genes, which are responsible for cytokines storm and RNA transcription. The COVID-19 and all RNA viruses can be controlled by inhibition of nuclear factor kappa-B, which is controlled by inhibition of hydrogen peroxide and inhibitor kappa-B kinase enzyme.
Breast cancer has ranked number one cancer among Indian females with age adjusted rate as high as 25.8 per 100,000 women and mortality 12.7 per 100,000 women. Diagnosis of Breast lesion has leaped rapidly from FNAC to molecular methods .In some institutes, the best possible cost effective diagnosis is given, whereas in others, molecular studies are done to provide the diagnosis . Immunohistochemical markers like ER, PR , Her2 neu, growth factor receptor -2, Ki- 67, progesterone receptor and p53 are used in breast cancer. Most commonly used among them are ER, PR and Her2 neu , which have array of use in subtyping , treatment and determining prognosis. ER(Estrogen receptor) serves dual roles in breast cancer by predicting favorable disease outcome and by facilitating tumor progression. Up-regulation of ER and/ or the selection of specific ER mutations are early events important for facilitating tumor progression. Along with estrogen receptor (ER), HER-2 is an important gene for molecular targeting treatment . As compared with HER2-negative tumors, HER2-positive breast cancer is aggressive subtype that demonstrates unique epidemiological, clinical, and prognostic differences with poor response to standard chemotherapy regimens. The HER2 gene amplification in the breast cancer is closely related to tumor-cell multiplication ,invasion ,high mitotic count and positive-lymph node metastases, resulting in focal progression and distant metastases leading to adverse survival outcome. Our study aims at correlating Her2 Neu with ER status, mitotic count , lymph node status, lymphovascular invasion.
Ovarian Carcinoma (OC) is the most lethal gynaecological tumour. While other female pelvic tumours such as uterine cervical cancer display a spectacular decline due to identification of early stages and precursors, the incidence and mortality of OC remains about the same for the past five decades. The main reason for this is the late clinical diagnosis in the majority of cases and the lack of reliable tumor markers for early stage neoplasms. The most common OC is the Ovarian Serous Carcinoma (OSC) characterized by its lack of symptoms during the early stages. Less common OC, Endometrioid Carcinoma (EOC) , Clear Cell and Mucinous Carcinomas (CCC and MC) become symptomatic in earlier stages due to symptoms outside the ovaries (pelvic masses, vaginal bleeding, infertility, abdominal pain). Our clinical-pathologic studies revealed that Stage I OC confined to the ovary(ies) are diagnosed in less than one third of OSC while the overall less common EOC, CCC and MC represent the majority of Stage I OC. Patients with OSC are older on average, are more often BRCA positive and may have a personal /family history of breast cancer. Patients with EOC, CCC and MC are younger on average, have histories of infertility and/or hyperestrogenism (endometrial polyps, hyperplasia, leiomyomas).. Patients with atypical endometriosis are at risk to develop EOC and CCC. Early diagnosis for the more aggressive OSC is occasionally made due to more frequent medical exams because of family history or previous breast cancer. Our study of Prophylactic salpingo-oophorectomy specimens by histologic, morphometric and molecular biology methods identified precursor/precancerous lesions in the ovarian and fallopian tube epithelium (tubo-ovarian dysplasia) adjacent to invasive cancer and in patients at risk for OC. These findings are shedding light into early ovarian carcinogenesis and may have implications in the choice of strategies for this still mostly elusive cancer.
Cervical cancer is the most frequent cancer among women in Senegal. However, there are few data concerning the human papillomavirus (HPV) types inducing neoplasia and cervical cancers and their prevalence in the general population of Senegal. The aim of this study is to determine the prevalence of HPV infection in Senegalese women aged 18 years and older in Dakar Region and three other regions. Cervical samples were collected from 498 women aged 18–80 years (mean, 42.1 years) in Dakar Region. Also, 438 samples were collected from three other regions: Thiès, Saint‐Louis, and Louga. The samples were screened for 21 HPV genotypes using an HPV type‐specific E7 PCR bead‐based multiplex genotyping assay (TS‐MPG). The prevalence of high risk (HR)‐HPV in Dakar Region was 17.4%. HPV 52 (3.2%) was the most prevalent HPV type, followed by HPV 31 (3.0%) and HPV 16, 45, and 53 (all 2.8%). In the Thiès, Saint‐Louis, and Louga Regions, the prevalence of HR‐HPV was 23.2%, 13.1%, and 19.4%, respectively. The study revealed the specificity of HPV prevalence in Dakar Region and other regions of Senegal. The observed patterns show some differences compared with other regions of the world. These findings raise the possibility that, in addition to HPV 16 and HPV 18, other HPV types should be considered for a vaccination program in Senegal. However, additional studies to determine the HPV type distribution in cervical cancer specimens in Senegal are required to further corroborate this hypothesis. J. Med. Virol. 86:248–256, 2014. © 2013 Wiley Periodicals, Inc.
Biological behaviour is still dilemma irrespective to highly advancements in tumor knowledge due to diverse and interacting underlying mechanisms, an issue that stimulates researchers, practitioners, and scientist to explore more and more thoughts, ideas, and mechanisms. Based on my experience in the cancer research, I have constructed the mirror image model that predicts cancer behaviour. The expression of biomarkers is a very important feature of biological cancer behaviour. In this model, the expression of two biomarkers using immunohistochemistry was implemented. We have previously published an article about the use of digital imaging techniques for better understanding of cellular reactivity, in which we showed how can the expression of biomarkers be changed from qualitative to quantitative through the use of imaging analysis properties provided by adobe Photoshop software. The idea depends in calculating the total pixels per image, then an option to select a color of the image to compute its distribution as pixels. The obtained number is divided by the total pixels in slide. The resulting number is recorded. Using these options gave us the possibility to shift our knowledge in following the biological behaviour of cancer (Al-Jarrah et al., 2010; Bani-Ahmad et al., 2018). However, we have previously conducted several studies to follow the biological activities of several diseases including diabetes and neurological diseases (Al-Jarrah et al., 2013; Alkhatib et al., 2013; 2014;Amawi et al., 2019;Ali Alsarhan et al., 2020).
Mesenchymal Stem Cells (MSCs) have been widely used in stem cell-based therapy due to their immunomodulatory and anti-inflammatory properties. They secrete many types of cytokines by paracrine secretion leading to this immunomodulation. The immunomodulatory effects of MSCs are further triggered by the activation of TLR receptors in MSCs, which is stimulated by pathogen-associated molecules such as LPS or double-stranded RNA from virus-like the HCoV-19. In December 2019, the whole world has encountered a new pandemic Novel Coronavirus disease 2019 (COVID-19) which is originated from China and spread all over the world in a few months. The Clinical situation of COVID-19 infection varies from mild fever to respiratory failure resulting in acute respiratory distress syndrome (ARDS) and death. Increased proinflammatory cytokine activation with detrimental alterations in the lungs has been suggested as a hallmark in the pathogenesis of infection. Since there is no effective cure or vaccine, primary prevention strategies such as avoiding close contact and attention to personal hygiene are strongly recommended. Recent studies have demonstrated that the first step of the HCoV-19 pathogenesis is that the virus specifically recognizes the angiotensin I converting enzyme 2 receptor (ACE2) by its spike protein and therefore ACE2-positive cells are infected by the HCoV-19 virus. Unfortunately, the ACE2 receptor is widely distributed on cells surface, especially the alveolar type II cells (AT2) and capillary endothelium.
Inter-organ communication plays a pivotal role in regulating whole organism physiological responses to changes in environmental factors such as nutrition. Over nutrition, or obesity, can lead to adipocyte dysfunction and is often associated with human diseases, including type 2 diabetes and many cancers. The Drosophila melanogaster ovary, a stem cell-supported organ, is highly responsive to dietary changes, showing a severe reduction in egg production when female flies are fed a protein-poor diet. This effect on egg production is mediated by nutrient-sensing pathways acting within the ovary and remote nutrient sensing by other tissues such as the fat body. We have previously shown that amino acid sensing specifically in adipocytes, the major cellular component of the Drosophila fat body controls germline stem cell (GSC) maintenance in adult ovaries. Reduced adipocyte amino acid transport leads to loss of GSCs by activation of the amino acid response pathway. We hypothesize that the amino acid response pathway mediates GSC loss by reducing translation of factors necessary for maintenance. The highly conserved AAR pathway further activates two downstream effects that may mediate its control on GSC maintenance: a global reduction in translation and selective up-regulation of ATF4 dependent transcription.
Both Breast and Uterus are highly sensitive to hormonal influences, normally related to their reproductive functions. Due to abundant Receptors in their tissues, hormones are capable of eliciting profound changes of breast and uterine tissues, including neoplasms. Prevention and therapy of Breast and Endometrial Cancers using hormones as an adjuvant therapy is successful but challenging as there are side effects to be avoided. Tamoxifen (Tam) is a non-steroidal synthetic triethylene estrogen derivative used successfully in the adjuvant therapy and prophylaxis of breast cancer. It binds to Estrogen Receptors(ER) in a manner similar to estradiol inducing a binding of Tam-ER complexes to the nuclear DNA resulting in a decrease of available unbound ER, exerting an antagonistic, antiestrogenic effect on breast tissue. Its effect on the uterus is more complicated as Tam acts both as an antagonist and an agonist of Estrogen. In the uterus the agonist effect is manifested by endometrial polyps, hyperplasia, leiomyomas, adenomyosis and occasional neoplasia. In the largest study published so far, endometrial tissue (from biopsies and Hysterectomies) from 700 patients treated with Tam for Breast cancer, 64% showed normal cycling or inactive/atrophic endometrium ; 24% had endometrial benign polyps with cystic glandular and/or mild hyperplastic glands, displaying a different histologic pattern from endometrial polyps seen in patients not treated with Tam; in 4.7% of cases, frankly malignant changes were identified, the majority serous carcinoma of high grade, less than one third low grade endometrioid carcinoma. The malignant endometrial tissue was found in polyps, not associated with hyperplastic or atypical glands as it is most often seen in endometrioid carcinoma of patients not treated with Tam. Endometriosis carcinoma is the most common gynecological cancer in the USA and in most of the industrialized world; its relationship with hyperestrogenism is well established although the carcinogenic mechanism is not yet clarified. Many reports of individual cases of high grade endometrial cancer including very aggressive carcinosarcomas have also been reported in Tam treated patients. Endometrial cancers were seen more often in older patients, and in those treated for a longer duration. Despite these unfavorable side effects Tam is still used for its beneficial effect in preventing and treating breast cancer. Recently however it was established that Aromatase Inhibitors (A.I.) stop the production of estrogen in post-menopausal women by blocking the enzyme Aromatase which turns androgens to estrogens, resulting in a decrease of the available Estrogen to stimulate ER positive breast cancer cells. The use of A.I. is therefore less associated with estrogen-agonist side effects; it may however have other side effects such as cardiac anomalies and osteoporosis. Tam and A.I. are still both considered effective and may be used in the prevention and adjuvant therapy of Breast Cancer.
Most of the cancers are still incurable human diseases. All malignant tumors are a heterogeneous population of cells with different biological properties. There are two dominant concepts to explain tumor heterogeneity: the theory of tumor stem cells (TSCs), also called the hierarchical model and the stochastic model. TSCs constitute only a small percentage (0.05-1%) of tumor cells within a tumor mass containing heterogeneous population of tumor cells within the tumor microenvironment. TSCs are closely related to pathological features which result in worse clinical prognosis. TSCs are distinguished by the pronounced expression of anti-apoptotic proteins and the high activity of chemoresistance mediators – ABC-1,2,5, desregulation of signaling pathways Notch, Hedgehog, Wnt. TSCs harbour endogenous resistance mechanisms against radiation and chemotherapy which gives TSCs a survival advantage over differentiated counterparts. The currently known 40 TSC surface markers can express on the hESCs, adult stem cells, and normal tissue cells. Of the 40 TSC markers, approximately 83% (33 out of 40 TSC markers) are rarely expressed on normal tissue cells. 9 of these are already approved as drug target molecules by FDA. A minor TSC subset with maximum resistance to conventional anticancer therapies plays a special role in metastasis. According to the literature, melanoma TSCs are characterized by expression of antigens such as CD44, CD271, and CD133. CD133 is the most frequently studied TSC surface marker in various cancers. In our study we identified TSCs among melanoma DTCs by CD133 expression. 47 bone marrow samples of patients with melanoma were analyzed before treatment by flow cytometry. Among them, stage IV was established in 42.6% of cases. The immunophenotype of the cells was characterized based on the expression of the following antigens: Syto41, CD45, HMB-45, CD133. Evaluation of the expression of antigens was performed within the nucleated cells of Syto41+. Among the evaluated bone marrow samples, the presence of Syto41+CD45-HMB-45+ cells was found in 57.4% of cases. Only in one case, the presence of Syto41+CD45- HMB-45+CD133+ cells was established. The percentage of this subpopulation in this sample was 1.28. It should be mentioned in most cases, patients had an advanced stage of melanoma. This may confirm that CSC marker-negative or marker-positive cancer cells could initiate tumor formation. As demonstrated in our study, flow cytometry with a specific antibody HMB-45 in combination with CD45 is a useful technique to assess BM involvement in melanoma. BM involvement was found in 57.4% of skin melanoma cases. In 28.6% of cases I stage disease was established, which confirms the aggressiveness of skin melanoma even in localized disease. BM as a niche for micrometastasis plays a key role in hematogeneous dissemination. The detection of early dissemination of the tumor process may be a step towards individualization of treatment in this category of patients. At the same time, the identification of cells disseminated in the bone marrow with subsequent testing for the presence of TSCs antigens opens up prospects for the development of methods for influencing melanoma on the TSCs. It is nown that diversity of TSCs may be generated by distinct stemness or reprogramming signalling activations, resulting in divergent expression patterns or TSC markers. Recent findings demonstrates that the TSCs can be newly generated from the differentiated non-TSCs by reprogramming mechanism: even TSCs with different characteristics could emerge. TSCs not only serve as the origin of tumor formation but also drive heterogeneity of cell composition inside the tumor and TSCs themselves. In our study the findings of CD57 and CD133 expression are evidence of TSCs heterogeneity and the complex hierarchical relations between the primary tumor and the dissiminated TCs.
The new modality oft the dedicated Mamma-CT is offering a robust and comfortable Examination of the breast. It is working without any compression and produces 3D-images of the breast without any superimposions. Therefore it is avoiding two of the major problems of conventional mammography: Pain for the examined women and superimposion of glandular tissue. Adding a very short examination time, extremely high resolution oft he acquired images and the facultativ usage of contrast-media, the new technology oft the Mamma-CT emerges to be one of the greatest invention of senological diagnostics in the last years. Despite the first impression of being nothing more, than a nice tool for further assessment and an evaluation method for complex microcalcifications or multifocal findings, the Mamma-CT has a lot of possibilities in daily routine and turns out to becoming a real problem solver. Due to its robustness, short examination time, high resolution of 0.15mm in an isotropic manner, great comfort and usability of contrast media it fills the great gap between conventional Mammographie / tomosynthesis / contrast-Mammographie (TiCEM) and MRI. Even more it has the potential of becoming the reference modality for patients with Breast-implants or the clinic of secreting/bleeding mamilla. In the first case, the Mamma-CT offers high-end imaging of the breast AND the implants in one exam - without any compromise in sensitivity / specifity or risk of damaging the implants due to compression. In the second case, the mammo-CT can be used as a 3D-high-resolution-imaging tool for a classic galactrography – a complete new way of diagnosing intraductal tumors, like papillomas. This talk shows the technological background, the physics and advantages of this modality. It helps you to compare it to the traditional technologies and classify it in the setup of a multimodality approach in modern senological diagnosis. It gives also some breathtaking examples of this fascinating modality and cases out of daily routine.
Introduction: large intestine cancer is that the third common cancer within the world. Regarding 3-5% of the patients area unit carrier of genetic syndrome with high risk of large intestine cancer (CRC) et al malignancy. 20-30% of the patients with new diagnosed large intestine cancer had a case history of large intestine cancer. The foremost common hereditary syndrome is kill Syndrome (HNPCC hereditary non-polyposis large intestine cancer). Alternative syndromes with accumulated variety of polyps embody Familial adenomatous polyposis (FAP), attenuated FAP and MUTYH associated Polyposis (MAP). Genetics: kill syndrome is characterised by a germline mutation at a defective deoxyribonucleic acid couple repair (MMR) genes, with a high level of microsatellite instability. The foremost common genes concerned within the syndrome area unit MLH1, MSH2, MSH6, PMS2 and EpCAM. FAP caused by APC cistron defects and MAP caused by a defect within the MUTYH cistron. Kill syndrome and FAP area unit genetic chromosome dominant, whereas MAP genetic chromosome recessive. Designation is created by genetic investigation, founder mutation and cistron sequencing. Cancer risk: Mutation carrier of the various varieties of the syndromes has accumulated risk of colonic and extra-colonic tumor. The time period CRC risk is calculable to be 50-80% in HNPCC and regarding 100% in FAP. The chance of the malignancy development is betting on mutation and cistron. Clinical setting: Dutch capital criteria and revised Bethesda criteria were developed to spot persons and families with high risk kind kill syndrome. Patients with FAP area unit characterised by thousands of polyps and MAP patients by 10-100 of polyps. Universal screening for kill syndrome: ought to patients with large intestine cancer or endometrial carcinoma bear screening by assay (IHC) or microsatellite instability (MSI) for kill syndrome. Affirmative, many recommendations embody the universal screening for all diagnosed patients below age seventy years. The police work recommendation and treatment with Empirin or cox2 are going to be mentioned. All the higher than points are going to be updated and mentioned throughout the lecture.
Although the papillary thyroid cancer (PTC) has a good prognosis, the metastatic disease negatively impacts the survival rate. Recent data have been postulated that the cellular reprograming verified during the metastasis can lead to cancer-stem cells (CSCs) formation, which are related to the therapy failure. In this sense, we identified that the LIMD2 gene is differentially expressed in PTC and, overexpressed in lymph node metastasis of patients carrying the BRAF V600E mutation, suggesting that this gene can be involved in CSC formation and, therefore, in therapeutic resistance. In order to investigate this hypothesis, we promoted the LIMD2 knockout in two cell lines from PTC (BCPAP – BRAF V600E and TPC1 – RET/ PTC) using the CRISPR/Cas9 system. Following validate the LIMD2 editing by TIDE and immunoassays, we analysed the expression CSC-related hallmarkers (SOX-2, OCT-3/4, NANOG, ALDH1A1 and CD44) using proteome profiler array, flow cytometry and High-Content Screening, the expression levels of thyroid-specific genes (FOXE1, NKX2, PAX8, TG and TPO) by qRT-PCR and multidrug resistance protein (MRP1) by Western blot. Results showed that the LIMD2 knockout promoted the down regulation of all CSC-related hallmarks, as well as MRP1 especially in BCPAP edit cells, suggesting that LIMD2 can be associated to the drug efflux. However, we observed an up regulation in the expression levels of all thyroidspecific genes in BCPAP edit cells, suggesting that LIMD2 is related to the CSC formation in PTC. We also analysed the LIMD2 involvement in drug resistance mechanisms. For this, we treated both parental and edit cells with acid hydrolysis extract of Agave sisalana (AHEAS), which cytotoxic activity was previously demonstrated. Results showed that the LIMD2 knockout increased the number of apoptotic/necrotic cells in both edit cell lines. Altogether, these data strongly suggest that LIMD2 expression can contribute with therapy failure by increasing the MRP1 expression through CSC formation dependent manner.
Cancer is a disease of the genome. For a long time, it has been established that cancer mutations are determinant to induce tumor genesis, but recent evidences also point to epigenetic alterations as direct causes of cancer. It is now widely accepted that epigenetic changes are key in the reprogramming of stem and somatic cells into cancer stem cells (CSCs), which constitute the only subset of cancer cells truly immortal and capable of supporting cancer progression. Recent evidences from our group have demonstrated how miRNAs act as potent drivers from pluripotency to expanded differentiation potential, while they block reprogramming from somatic to stem cells. Mechanistically, we have described that these effects are mediated by direct repression of de novo DNA methyltransferases (Dnmt3a and Dnmt3b), leading to a resetting of the epigenetic memory. Given that experimental induction of pluripotency and tumor genesis entail obvious similar pathways, here we speculate that epigenetic changes induced by such miRNAs might unlock the cellular differentiation programs that are normally inactivated in cancer stem cells and at the same time, block the reprogramming from somatic to cancer stem cells, therefore dropping the CSC population in the tumor. Our hypothesis, if confirmed, would shed light on the differentiation-based antitumoral therapy and present those microRNAs as a promising tool for directly confronting the tumormaintaining and regeneration capability of cancer cells.
