Cancer Studies and Molecular Medicine – Open Journal
Editor- In-Chief: Pradeep Garg, PhD Title proper: Cancer Studies and Molecular Medicine – Open Journal Subject: Cancer Studies Publisher: Openventio Publishers Dates of publication: 2014 Frequency & Medium: Half-yearly , Online Language: English Country: India Indexed by: CROSSREF , ROAD , THE KEEPERS Title DOI of the Journal: http://doi.org/10.17140/issn.2377-1518
From Elegance to Complexity: The Intricate Dance of Myometrial Stem Cells Transforming into Leiomyoma Stem Cells: Unraveling the Symphony of Genetic and Epigenetic Refinement
Uterine leiomyomas (LM), commonly referred to as uterine fibroids (UFs), pelvic tumor in women of reproductive age globally and are main indicators of hysterectomies if become symptomatic. The progression of uterine LM involves a complex interplay of hormones, stem cells, growth factors, and genetic/epigenetic irregularities. Both endometrial and myometrial stem/progenitor cells play pivotal roles in the uterus’ response to hormonal stimuli and return to its basal state. LM, arising from a single stem cell of smooth muscle cells with acquired mutations, exhibit diverse cellular transcriptomic patterns influenced by genotype. Affecting over 70% of women at some point in their lives, with significant clinical symptoms, such as pelvic pain, infertility, and heavy uterine bleeding. Recent literature underscores the potential importance of LM stem cells and their paracrine interactions with specialized cells, connecting the gap between medications targeting leiomyoma expansion and potential eradication strategies. Keeping these points in view, this review discusses the current understanding of the involvement of myometrial stem/progenitor cells and the genetic and epigenetic changes occurring in these cells during the pathogenesis of uterine LM.
Complete Remission of Multiple Pulmonary Metastases of Endometrial Adenocarcinoma Treated with a Mixture of Low Molecular Weight Fucoidan and Canvaria gladiata Extract: A Case Report
Endometrial cancer (EC) is the most common malignant tumor in post-menopausal women, and the lung is one of the organs to which endometrial adenocarcinoma metastasizes. Chemotherapy is helpful for various malignancies, but not all are successful. A 71-year-old-Japanese-woman was diagnosed with metastatic lung cancer stage IV of primary endometrial adenocarcinoma. She received chemotherapy and hormone therapy after a total hysterectomy and pelvic lymphadenectomy. Subsequently, she visited this clinic for a second opinion as the metastatic lung cancer had repeated remissions and recurrences. Here, the authors report a case in which complete remission of metastatic lung cancer was achieved by using a product containing low molecular weight fucoidan extract (LMF) and Canavalia gladiata extract (CG) (LMF-CG) in combination with Medroxyprogesterone acetate (MPA) hormone therapy.
Low molecular weight fucoidan extract (LMF)
Precision Drugs are Needed for Precision Medicine to Work
target the right treatments for the right patients at the right time. However, it needs precision drugs with molecular structures that interact with precisely defined disease targets to do so.
National Consensus for Screening, Diagnosis and Management of Hepatocellular Carcinoma in Panama, 2022
Introduction Hepatocellular carcinoma (HCC) is considered the main primary neoplasm of the liver and its incidence is expected to increase in the next years. HCC is frequently associated with chronic liver disease secondary to hepatitis B or C infections, as well to alcohol abuse, fatty liver and metabolic syndrome. Multidisciplinary and individualized management has been shown to improve clinical outcome; nevertheless, in Panama and others Latin-American countries, there is no clear consensus for the management of this disease. Methodology Using Appraisal of Guidelines for REsearch and Evaluation II (AGREE II) methodology and the Institute of Medicine (IOM) criteria, we developed a multidisciplinary consensus for the management of hepatocarcinoma patients in Panama. Results This document synthesizes the current evidence on risk factors in conjunction with recommendations on the management of early, advanced and terminal disease. All healthcare personnel involved in the approach and treatment of hepatocarcinoma in Panama can find utility and applicability in their daily practice. Conclusion Here, we present the first National Consensus for the Screening, Diagnosis and Treatment of Hepatocellular Carcinoma in Panama.
Cancer Disease-Oriented-Drug Development Examples
The history of cancer medical treatments goes up to 1908 with the use of arsenic in this disease. An intermediate milestone was the discovery, in 1943, of an amazing tumor response using nitrogen mustard in a patient with a radio-resistant lymphoma. Chemotherapy really born with this achievement, and a plethora of antitumor agent’s came to age after 1948 till nowadays. Here, some examples of recent disease-oriented drug development approaches are presented and analyzed, as well as present limitations and challenges raised by each one.
Equilibrium between cell survival and death is important for normal cell homeostasis and development and also for inhibiting pathologies particularly cancer. Anastasis is a natural cell recovery phenomenon that rescues cells from the brink of death or a mechanism by which cells recuperate from apoptotic lesions and return to its normal active and functioning state. Programmed cell death (apoptosis) was known to be an intrinsically irreversible cascade that commits cells to a rapid destruction. However, recent studies have demonstrated the possibility of recovering dying cells even at the late stages. Anastasis uses the usual pro-metastatic and pro-survival factors to inhibit apoptotic progression. Epithelial mesenchymal transition (EMT) activation and its related modulators is not only linked with cellular metastasis and survivability but also widely associated with the stemness of cancer cells.
Even though cancer researchers nowadays are trying to develop many key cellular pathways susceptible to be tackled by therapeutic approaches, we are far from being able to consider some cancers as curable diseases in general terms. From a pharmacodynamic point of view, the main potential molecular targets involved are driver oncogenes, tumor suppressor genes, growth factors and their receptors, transcription factors, tyrosine kinases, and cell adhesion molecules. If we consider possible targets at higher organization levels, we can intervene in aspects such as chromatin organization, tumor microenvironment, angiogenesis, apoptosis, senescence, mitochondria metabolism, and immune pathways.
Pathology Hiding in Plain Sight: The NF1 Plasma Membrane
The passive voice and the active voice: for example, is it a matter of “at” or “to?” The NF1 gene product, neurofibromin (Nfn), in its interaction with the oncoprotein, Ras, does something to the cell’s plasma membrane (PM); the reactions in question do not merely happen at the cell’s PM. Moreover, what the Nfn does to the PM in NF1 cells has been seriously underestimated because of yet another perspective issue. The vast majority of publications on the membrane-bound interaction of Nfn and Ras have been from the perspective that, first and foremost – if not exclusively – the NF1 gene is considered a “tumor suppressor gene.” This is rather narrow, respecting the ancient origin and very highly conserved nature of the NF1 alphabetical code, and the intuitive understanding that the vast majority of eukaryotic species are not at risk for tumors or cancer.
The Phenotype Landscape of Cancer in the Genotype Era
Some tumor types such as testicular cancer, leukemia and lymphomas, have their origin in cells that comport a common embryonic origin. This phenomenon was “unconsciously” the roadmap to treat and cure them by classic chemotherapy. The cells are very chemosensitive indeed as they are “immature” in origin. Chemotherapy has also positively impacted the overall survival of some pediatric and adolescent cancers (leukemias, lymphomas, bone tumors) and in many other adult ones such as breast, ovarian, head and neck and colorectal cancers. Despite everything, we also face other difficult to treat cancers which remain chemo resistant (lung, melanomas, pancreatic, biliary tract cancers as the most representative ones.
Oligo-Metastatic Carcinoma Cervix: A Few Do Extremely Well
The consequence of metastatic carcinoma cervix is regarded to be poor. We present three patients with carcinoma cervix who relapsed in the paraaortic nodes, lungs and vertebra. All of them had oligometastatic disease and were treated with chemotherapy to the lung lesion and radiotherapy to the bone lesion and paraaortic nodes. After more than 5-years they are disease free and on regular follow-up.
Historically, natural products played a forceful role in human treatment ailments. Nowadays, natural products include a large part of current pharmaceutical agents, mostly in the field of cancer therapy. The main aim of this review is to provide a comprehensive summary of the most known natural product used as anticancer globally, including various other natural products. Many of these natural product appears to act through an anticancer mechanism. Overall, natural product research is a vigorous tool to discover novel biologically active components with unique mechanisms of action. Given the diversity of nature, it is sensible to indicate that chemical leads can be produced that are able to interact with most therapeutic targets. This review creates a solid foundation for further study these natural products with additional research and study.
Deep-Ultraviolet Raman Spectroscopy for Cancer Diagnostics: A Feasibility Study with Cell Lines and Tissues
Background Deep-ultraviolet resonance Raman spectroscopy (UVRS) offers significant advantages over visible and near-infrared Raman spectroscopy for biological applications, including cancer identification. Cancer is the second-leading cause of death in the United States. Early diagnostics plays a crucial role in providing the best chances for an afflicted individual to seek successful treatment opportunities. Current methods for diagnosing various forms of cancer are both expensive and invasive. As such, the objective of this study is to explore the feasibility of UVRS for discrimination of cancerous tissues and cancer cells from normal samples. The safety issues of using ultraviolet light for human applications are analyzed. Methods Cancerous brain tissues from nonobese diabetic/severe combined immunodeficiency (NOD-SCID) model mice injected with 435-tdT cells (human adenocarcinoma breast cancer cells) at known locations and adjacent normal brain tissues as well as normal and cancer (adenocarcinoma PC-3) prostate cells were studied using UVRS. The obtained Raman spectra of the healthy and cancerous samples are compared in order to identify biochemical differences between them. Results The obtained spectra reflect biochemical differences which occur between the healthy and malignant samples in both brain and prostate cancers. UVRS provides distinctive resonance signatures of major biochemical components, including proteins and nucleic acids, and it does not suffer from fluorescence interference, nor does it require high laser power levels for excitation. These advantages allow for clear and effective spectral discrimination between samples. Conclusion Our results suggest UVRS should be considered for cancer identification, and is safe for use within humans. The proposed innovative approach has significant potential for cancer imaging and real-time tissue discrimination during surgery.
Deep-ultraviolet resonance Raman spectroscopy
Engaging African Americans in Breast Cancer Prevention Strategies: A Partnership Between a Community Cancer Center and the African American Community in Delaware
Although breast cancer incidence has been stable for non-hispanic whites since the early 2000s, incidence rates of invasive breast cancers in African Americans (AA) are rising (0.9%/ year 2005-2014).1 This is especially true for younger black women. Breast cancer incidence in black women under 45 years has recently surpassed that of their white counterparts.2 This is concerning as breast cancer specific mortality is higher in African Americans than all other races. Although many breast cancer risk factors have been identified, there is a need to develop breast prevention strategies specifically targeting the AA community.
The Emerging Spectrum of Early Life Exposure-Related Inflammation and Epigenetic Therapy
Early life exposure to a variety of insults during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life. During this process, inflammation triggered by a variety of adverse exposures plays an important role in the initiation and development of many types of diseases including tumorigenesis. This systematic review article summaries the current knowledge about the role and mechanism of inflammation in development of diseases. In addition, epigenome alteration related to inflammation and treatment options using epigenetic modifiers are highlighted and discussed.
A Case of Choroidal Metastasis from Small-Cell Lung Carcinoma
A 74-year-old man visited to our hospital due to severe visual disturbance in his left eye for recent one month. Fundoscopy demonstrated the serous retinal detachment at the nose side of the left eye.At the same time, chest X-ray demonstrated a mass measuring 4 cm in size at the left lower lung field (Figure 2, arrow) and thoracic computed tomography (CT) depicted the mediastinal lymphadenopathies. On Hematoxylin-Eosin stain, both specimens obtained from right B10 by transbronchial lung biopsy (Figure 3A, 400X) and subcarinal lymphnodes (Figure 3B, 400X) by endobronchial ultrasound-guided transbronchial needle aspiration demonstrated abundant atypical cells with high nuclear cytoplasmic ratio. Those cells were positive for both CD56 (Figure 3C, 400X) and TTF-1 (Figure 3D, 400X), he was thus diagnosed with small cell lung carcinoma (SCLC).
Bilateral Symmetric Thalamic Metastasis in a Patient with Small Cell Lung Cancer
A 68-year old woman was referred to our hospital because of dry cough with persistent numbness in the extremities. Chest roentgenogram showed right hilar tumor with mediastinal lymphnode and brain magnetic resonance imaging (MRI) revealed multiple tiny nodules. After performing the transbronchial needle aspiration obtained from subcarinal lymphnode, she was diagnosed with small cell lung cancer (SCLC) accompanied by multiple brain metastasis (clinical stage IV: T4N3M1). After completion of four cycles of chemotherapy, the size of lung lesion was regressed together with complete resolution of brain lesions, and she discharged uneventfully. However, her numbness was remained. Four months later, she was hospitalized again for severe numbness in her trunk and extremities. Brain MRI (contrast-enhanced T1-weighted image) demonstrated new symmetric metastatic lesions in bilateral thalamus (Figure A and B) as well as left putamen. Another two months later, numbness exacerbated and spread from the top to toe with the growing of primary and bilateral thalamic metastatic lesions on computed tomography (CT) (Figure C and D). In spite of whole-brain irradiation, she had suffered from severe numbness, and died of obstructive pneumonia. To our knowledge, this is the first case of bilateral symmetric thalamic metastasis in SCLC with refractory numbness over the whole body.
A Rare Case of a Urachal Mucinous Cystic Tumour of Low Malignant Potential
A persistently patent urachal remnant can lead to neoplastic transformation. Urachal tumours occur most commonly as glandular neoplasms which are classified as benign, non-cystic or cystic. However, the literature on cystic urachal tumours is extremely limited. Here, we describe a case of a 59-year-old male who presented with a mucinous cystic tumour of low malignant potential of the urachus and review the current literature. In addition, we summarise the classification system on cystic urachal tumours which has been proposed by Amin et al and modified in the World Health Organisation (WHO) 2016 Classification of Tumours of the Urinary System and Male Genital Organs.
Dosimetric Characterization of an Abscopal Response in a Patient With Oligometastatic Melanoma Undergoing Concurrent Treatment With Pembrolizumab and Stereotactic Body Radiotherapy (SBRT)
Recently, preclinical and clinical evidence has shown that a synergy may exist between radiation and immune check-point therapies such as pembrolizumab. Radiation has been shown to activate the immune system, and in combination with immunotherapy may lead to systemic anti-tumor responses. However, the exact dose regimens needed to induce synergistic responses are unclear. Here, we report a dosimetric characterization of a patient treated with stereotactic radiation in combination with immune check-point therapy.
The Emerging Role of p27 in Development of Diseases
The cell cycle regulation and tumor suppressor p27 encoded by CDKN1B plays a key role in many cellular events.1-3 p27 is a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors, which functions to negatively regulate cell cycle progression at the G1/S boundary in response to antiproliferative stimuli. In addition, numerous p27 functions, not related to CDK inhibition, have been described. For instance, cytosolic p27 plays a role in the regulation of cytoskeleton assembly/disassembly, therefore, regulates the cell morphology and movement. In addition, p27 is involved in apoptosis and autophagy modulation. Mutations, abnormal expression and mislocalization of p27 have been found in many diseases suggesting the important role of p27 in the pathogenesis of diseases. Human p27 gene (CDKN1B) was cloned in 19947 and mapped to chromosome 12p13. Later on, p27 mutations were discovered in several types of human cancers including breast cancer, sporadic parathyroid adenomas, endocrine neoplasia, small intestine neuroendocrine tumors
Classifying Lung Adenocarcinoma and Squamous Cell Carcinoma using RNA-Seq Data
Background: Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are two primary subtypes of non-small cell lung carcinoma (NSCLC). Currently, the most widely used method to discriminate between LUAD and LUSC is hematoxylin-eosin (HE) staining. However, this method is not always able to precisely diagnose LUAD or LUSC. More accurate diagnostic approaches are highly desired. Methods: We propose to use gene expression profile to discriminate a patient’s NSCLC subtype. We leveraged RNA-Seq data from The Cancer Genome Atlas (TCGA) and randomly split the data into training and testing subsets. To construct classifiers based on the training data, we considered three methods: logistic regression on principal components (PCR), logistic regression with LASSO shrinkage (LASSO), and kth nearest neighbors (KNN). Performances of the classifiers were evaluated and compared based on the testing data. Results: All gene expression-based classifiers show high accuracy in discriminating between LUSC and LUAD. The classifier obtained by LASSO has the smallest overall misclassification rate of 3.42% (95% CI: 3.25%-3.60%) when using 0.5 as the cutoff value for the predicted probability of belonging to a subtype, followed by classifiers obtained by PCR (4.36%, 95% CI: 4.23%-4.49%) and KNN (8.70%, 95% CI: 8.57%-8.83%). The LASSO classifier also has the highest average area under the receiver operating characteristic curve (AUC) value of 0.993, compared to PCR (0.987) and KNN (0.965). Conclusions: Our results suggest that mRNA expressions are highly informative for classifying NSCLC subtypes and may potentially be used to assist clinical diagnosis.
Copyright (c) 2017 Cancer Studies and Molecular Medicine – Open Journal
How Target Therapy can Induce Cardiotoxicity: The Onco-Cardiologist Point of View
The life expectancy of an oncological patient has been increased significantly decades due to the evolution of cancer therapies. The aim of this paper is to review how these new target molecules, which have a direct impact on the cancer cell as opposed to the classical chemotherapy, known to all of us for a long time. How do they act specifically? What are their cardiotoxic effects at a short and long time period? How can they be monitored? How can they be prevented and treated? And above all, how can we prevent an oncological patient to become a cardiovascular one later on, due to induced cardiotoxicity caused by oncological therapies. We have to treat our patients as a whole and not only, target therapy to one of the pieces of the puzzle.
Is it Time to Start Using Mitochondrial DNA Copy Number as an Indicator of Health and Diseases?
Clinical biochemistry and pathology have contributed too many assays for diagnosis and prognosis of human health and diseases. Bedside biochemistry has revolutionized modern medicine and the invention of new generation biosensors have educated the patients like never before. Although, there are many gadgets which are available for monitoring the blood glucose in the patients with metabolic syndromes, hardly any assays can accurately predict and aid in early detection of metabolic syndrome. By the time a person is diagnosed and treated for metabolic syndrome, molecular and pathological damages further push the patient towards the metabolic syndrome. Early detection and early treatments are necessary to further revolutionize the field of Medicine.
Neurofibromatosis Type I and Multiple Gastrointestinal Stromal Tumors: A Unique Identity
Von Recklinghausen’s disease (VRD) is a genetic disorder characterized by the growth of multiple noncancerous tumors of nerves and skin (neurofibromas) and areas of hypo or hyperpigmentation of the skin. It is also known as Neurofibromatosis type I (NF1) and represents one type of VRD. It is an autosomal dominant disorder with a rate of occurrence of 1 in 3000 in the general population.1 The cause of NF1 is a mutation in the NF1 gene, located at the chromosome 17q11.2, which encodes the tumor suppressor gene, neurofibromin. Loss of neurofibromin function results in activity of Ras oncogene and consequently tumor formation.
Dysadherin: A Novel Oncogenic Molecular Biomarker in Oesophageal Cancer
Dysadherin or FXYD5 is a transmembrane glycoprotein, identified for the first time in 2002 by a team of Japanese researchers.1 Although, it is generally accepted that most of its action is derived from the increased maximal velocity (Vmax) of the Na+-K+-ATPase that promotes, there are several actions of dysadherin that cannot be attributed to its interaction with the Na+-K+-ATPase.2 Dysadherin is a well-described cancer-associated protein and a potential oncogenic molecular target with promising future significances. It has been distinctly shown, in both the cases of in vivo and in vitro studies, that when expressed in malignant tumours, it signifies augmented tumorigenesis with enhanced metastatic potential and haematogenous spread and is thus linked to poor prognosis.3,4 On the contrary, studies based on human cancer cell lines have demonstrated that introduction of small interfering RNA (siRNA) against dysadherin leads to downregulation and subsequent membranous underexpression of dysadherin, instigating accordingly decreased collective and individual cell motility with subsequent inhibition of tumour aggressiveness and metastatic potential.5 Its main interaction in carcinogenesis takes place with E-cadherin (epithelial cadherin); the most important adhesion molecules of the cadherin family. E-cadherin is involved in cancer development in more than 90% of human cancers, as most are carcinomas of epithelial origin. E-cadherin mediates homophilic cell-to-cell adhesion and promotes adherence between neighboring epithelial cells; its decreased cellular expression is hence associated with enhanced disconnection and dispersal of epithelial cells, promoting cell detachment from the primary lesion and consequently exhibiting increased metastatic potential.
Rounding Down Chemotherapeutic Agents to the Nearest Vial Size as a Cost Containment Measure
Background: High cancer treatment costs significantly affect health care expenditures. Drug waste reduction of costly drugs can reduce the treatment cost. Methods: A retrospective study conducted at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Adult patients above age of 14 years old who received chemotherapy between March 1st to March 31st, 2015 were included. Maximum dose rounding allowed was up to 10% for palliative intent and 5% for curative intent. Patients demographics, diagnosis, treatment intent (cure or palliation), ordered dose, rounded dose, vial size, number of vials that could be saved and expected cost saved per month were calculated and recorded. Results: A total of 305 patients received 973 doses of intravenous chemotherapy drugs during the study period. Orders of 352 doses could be rounded to the nearest vial size with a 10% dose deviation for palliative intent and 5% for curative intent. The projected savings for 1 month was calculated to be Saudi Riyals (SR) 14,720.95 for 5% rounding limit and SR 53,157.50 for 10% rounding which will account to an estimate of SR 814,514.40 of drug cost savings per year. Anti-cancer drugs with the most drug wastage due to non-rounding to the nearest vial size were trastuzumab, cyclophosphamide, etoposide, methotrexate, fluorouracil, paclitaxel, oxaliplatin, doxorubicin, bortezomib, and cytarabine consecutively. The highest costs savings when rounding the doses to the nearest vial size up to 5% for curative intent was associated with rituximab, followed by fludarabine and paclitaxel. Bevacizumab, cetuximab, and carfilzomib have resulted in the most cost savings when the rounding limit was set to 10% for palliative intent. Conclusion: Dose rounding of the ordered dose to an amount within 5% for curative intent and 10% for palliative intent to the nearest vial size has resulted in a valuable cost savings through reduction of drug wastage without any expected compromise in efficacy.
Gastrointestinal Stromal Tumors: Innovation from Diagnosis to Treatment Based on 15 Years of Experience of a Peripheral Hospital in Portugal
Aim: To investigate fifteen years of experience, in managing GISTs, according to best clinical practice, on a peripheral Portuguese Hospital. Define the behavior of GIST’s and the association between the histological, immunehistochemistry characteristics and disease progression. Question if the optimal treatment was delivered in GIST patients, based on medical evidence, where limitations on evaluating molecular signatures exists. Methods: A retrospective analysis of cases treated in Hospital of Entre Douro and Vouga from 1 January 1999 to 31 December 2014 was performed. Demographic characteristics were evaluated related to tumor characteristics according to the National Institute of Health criteria and disease progression. All patients were evaluated in a multidisciplinary team. An expert treatment decision was made according to the National Institute of Health criteria of Gastrointestinal stromal tumor’s risk of recurrence after surgery. Statistical study was performed using SPSS version. Results: Sixty-three cases were evaluated, 61.9% in female patients and 38.1% male. The median age at diagnosis was 69 years. A progressive increase in the incidence of GISTs was documented since 1999 to 2014. The most common source locations was the stomach with forty-five patients (71.4%), When assessing the Mitotic count, 27% was superior to 5 mitosis/50HPF and 73% was inferior to 5 mitosis /50HPF. Sixty-two patients underwent surgery with R0 resection rate of 94% Immunohistochemistry was performed in all patients, and sixty-one patients were positive for CD117. Only two patients were CD117 negative. No KIT gene mutation analysis was performed. Regarding the biological risk of recurrence or metastasis, according to the National Institute of Health, 25,4 % of the patients had a very high risk, 19,0% had an intermediate risk, 34,9% had a low risk and 20,6 % had a very low risk. Of the 63 patients, 25.4% (n=16) were submitted to adjuvant treatment with imatinib (400 mg/ daily) during 3 years. Only 7.9% (n=5) received palliative treatment with imatinib and sunitinib. Only in 11% of the patients the disease progressed (median time to progression of 36 months). The mortality rate was 12.7% (n=8). Fifty-five patients were alive (87.3%) at the end of this retrospective study. Conclusions: Mutation analysis was not performed, which might have influenced the treatment and prognosis. Optimize therapy based on molecular signatures are extremely important for a cost-effective treatment.
Current Status of Anti Epidermal Growth Factor Receptor Therapy in the Curative Treatment of Head and Neck Squamous Cell Carcinoma
Squamous cell carcinoma of head and neck is the most common malignancy of the upper aero digestive tract in the world. In this article, we attempt to summarize the role of antiepidermal growth factor therapy (EGFR) in the treatment of locally advanced head and neck squamous cell carcinoma. Cetuximab plus radiotherapy is a reasonable alternative in patients who cannot tolerate standard concurrent chemoradiotherapy (CTRT). There is no benefit by adding targeted therapy in addition to standard CTRT. Trials evaluating the role of targeted agents in the adjuvant setting showed no benefit in patients with high risk features; in addition to standard post-operative CTRT. Role of adjuvant monoclonal antibody in patients with intermediate risk factors is being evaluated.
Potential of Molecular Imaging to Advance Molecular Medicine
Molecular imaging is a technology that allows for non-invasive interrogation of physiological and biochemical processes in the body. Over the years, the use of Molecular Imaging is on the rise, especially towards diagnosing cancer and monitoring treatment. Molecular Imaging has a significant role to play at preclinical and translational stages in the field of Molecular Medicine. Molecular Imaging tools include Magnetic Resonance Imaging (MRI), Magnetic Resonance spectroscopy (MRS), Computed Tomography (CT), Positron Emission Tomography (PET), Ultrasound (US), and Optical Imaging among many more. While CT and MRI remains as first-line tools for diagnosing ailments by the clinicians, pre-clinical and clinical use of Positron Emission Tomography (PET) is steadily rising. Newer PET probes are being developed and being evaluated for their effectiveness in patient care and disease management. While this technology has tremendously benefitted the pre-clinical research, it has also become one of the indispensable tools in the clinic. In addition, now PET is proven to be quite helpful in expediting the drug development and discovery efforts. Over the last two decade, a significant progress is made towards expanding the role of Molecular Imaging. It plays significant role in Oncology, Neurology, ageing, drug abuse, and cardiac applications. With increased acceptance of this modality in the clinics around the world, there is a growing interest in utilizing PET to target biological systems and to assess the outcome of certain treatments in patients.
Prostate Cancer Trends in Developing Countries
Prostate cancer is the commonest cancer in USA and most European Countries and is the 2nd commonest cancer among males globally. An estimated 1.1 million men worldwide were diagnosed with prostate cancer in 2012, accounting for 15% of the cancers diagnosed in men. Incidence of this disease varies more than 25-fold worldwide; the rates are highest in Australia/New Zealand and Northern America (ASR 111.6 and 97.2 per 100,000 respectively), and in Western and Northern Europe, because the practice of prostate specific antigen (PSA) testing and subsequent biopsy has become widespread in those regions.
The Proportion of ALDEFLUOR-Positive Cancer Stem Cells Changes with Cell Culture Density Due to the Expression of Different ALDH Isoforms
A significant number of discrepancies exist within the literature regarding ALDEFLUOR- positive stem cell populations in cell lines. We hypothesized that these inconsistencies resulted from differences in culture conditions, particularly cell density. We cultured several colon cancer cell lines (N=8) at high and low densities and found a significant decrease in ALDEFLUOR-positive cell populations at high density. However, we found no changes in the CD166-positive stem cell population, self-renewal, or cell cycle distribution of cells cultured at different densities. Interestingly, when we sorted both ALDEFLUOR positive and negative populations from the different density cultures, we identified a significant number of Aldehyde dehydrogenase (ALDH) isoforms whose expression was decreased in ALDEFLUOR-positive stem cells cultured at high density. This novel finding suggests that multiple ALDH isoforms contribute to ALDEFLUOR activity in colon cancer stem cells and decreases in ALDEFLUOR- positive stem cells at high cell density are due to decreased expression of multiple ALDH isoforms. Thus, designing therapeutics to target ALDEFLUOR-positive cancer stem cells may require inhibition of multiple ALDH isoforms.