Day 1 full schedule
November 25, 2020 @ 16:50 - 21:40
Yash Shrinivas BichuBiotechnologist
DY Patil Deemed to Be University, India
Cancer treatments including radiation therapy, chemotherapy etc. have been considered to be the main focus of cancer therapy. However, the resistance of cancer cells to all kinds of chemotherapeutic drugs and targeted drugs has become ubiquitous, and around 80-90% of deaths in cancer patients are attributed to drug resistance. Plethora of reports have suggested Cisplatin resistance in cervical cancer cells. Due to chemoresistance of established anti-cancer drugs, there is an immediate requirement to find new therapeutic methods for treatment of cervical cancer. Ritonavir, an Anti-HIV drug has been shown to have anti-cancer activity in different kinds of cancerous cells. The highlight of this research project was to study the drug repurposing potential of Ritonavir by using the technique of molecular docking to identify potential gene targets for drug repurposing and combinatorial impact of Cisplatin with the Anti-HIV drug Ritonavir using in vitro model of cervical cancer. Computational analysis using molecular docking was performed using AutoDock Vina and comparative evaluation was done by docking various HIV protease inhibitors including Ritonavir to potential target genes in cervical cancer cells. All the target genes exhibited good affinity towards Ritonavir and highest affinity was exhibited by the protein CYP450 3A4.Cytotoxic studies of Ritonavir and Cisplatin were performed on HeLa, a cervical cancer cell line. The IC50 of Cisplatin and Ritonavir was found to be 0.5230µM and 1.115µM, respectively for an incubation period of 24 hours with the drug. Significant morphological alterations were observed when HeLa cells were treated with different concentrations of Ritonavir. The combinatorial impact of both these drugs is yet to be established. We can state conclusively that Ritonavir seems to be a promising drug repurposing candidate for therapeutic treatment of cancer based on in silico and in vitro studies.
G.P. TalwarDirector Research
Talwar Research Foundation, India
A stage arrives in several malignancies, when metastasis have occurred all over in the body. No surgical removal is feasible, nor focussed radiation therapy. Patients are no more responding to the available drugs. At this advanced stage, many cancers express ectopically the embryonic hormone, Human Chorionic Gonadotropin (hCG) that promotes further growth of cancer. Humanized antibodies against hCG ± complement arrest the growth of such cancers.
We have examined 3 such cancers: Lung, Bladder and Liver. In each case our Monoclonal Antibody PIPP was effective in killing all these cancer cells plus complement. Curcumin attached to PIPP was even more effective. We therefore considered making of a recombinant immunotoxin, in which Fab of PIPP is linked to Sarcin, a potent ribotoxin. It could be made in large amounts industrially for wider use. In order to avoid repeated use of immunotoxin, and to back it up for long time cure, we have also genetically engineered a vaccine against hCG, which has already been passed on to a Biotech company.
Liquid Biopsy : An innovative noninvasive technology in the era of personalized medicine for diagnosis and therapy of Cancer
Pravin D. PotdarJaslok Hospital & Research Centre
Jaslok Hospital & Research Centre, India
Cancer diagnosis and therapy have been drastically changed due to development of innovative technologies in the field of genomic, proteomic and bioinformatic. Nowadays, genomics intervention, targeted or personalized therapy have gained great popularity to ensure the better effective treatment for cancer patients. The use of tumor biopsy for genomic profiling often provides only a snapshot, in addition, it is an invasive process. Other ways, it is very difficult to get the tissue for monitoring therapy of cancer patients. Liquid biopsy is one of the best alternative and non-invasive innovative technologies established by various scientists working in the field of cancer Research. Liquid Biopsy containing Circulating Tumor Cell (CTCs) and Circulating Tumor DNA (ctDNA) have been proved a very beneficial solution for overcoming this problem with tissue biopsy. Overall, it has shown that liquid biopsy containing CTCs and ctDNA can exactly represent the in vivo counterpart of the tumor tissue inside the patient body. CTCs has also been studied as a broad prognostic factor for various solid tumors including breast, lung , prostate and colon cancer. However, further study is needed to refine these results in view of cancer therapy & cure. Early detection of CTCs have been postulated to be useful in identifying increased risk of metastasis cancer which provides the opportunity to devise a customized adjuvant therapy in patients harbouring operable or locally advanced metastatic cancer. Various technologies have been developed for enumeration and molecular characterisation CTCs from liquid biopsies of metastatic cancer patients to know the exact stage of metastasis and precise therapy to target cancer cells for cure of this disease. It has been seen so far that it will be a novel technology to evaluate, diagnose and treat cancer in near future by using liquid biopsy testing. The current keynote address will be directed towards exploring the diagnostic, prognostic as well as predictive potential of liquid biopsy containing CTCs and ctDNA for evaluation and monitoring the therapy for metastatic cancer. In spite of the big role of CTCs & ctDNA in diagnosis and therapy of metastatic cancer, its routine use for clinical application is still not widespread. The setting of appropriate standards to validate the role of liquid biopsy in diagnostic & therapy of metastatic cancer is the need of today’s cancer research program.
Janet Premlata JeyapalCEO
Dr Jeyapaul Cancer Foundation Trust, India
Whether it is to target cancer cells or microbial resistance precision medicine plays an important role. Thousands of inhibitors and anticancer and antimicrobial agents are churned from various laboratories worldwide. Yet only one or two inhibitors are effective in clinics – this Is because precise inhibitors are not targeted to the right group
In our laboratory we synthesized silver nanoparticles and gold nanoparticles
Silver nanoparticles were studied to understand whether nonpathogenic microbial supernatsntd could provide a variety of nanoparticles shape and sizes that could be effective against a wide variety of resistant pathogens. It is known a wide variety of shapes and sizes of silver nanoparticles is required to combat resistance of spectrum of pathogens.This is something currently achieved only by chemical synthesis of nanoparticles. This is not eco-friendly. We compared two non pathogenic strains of microbial population to assess synthesis of nanoparticles against gram negative and gram positive organisms.
Gold nanoparticles are valuable in targetted photothermal ablation of cancer stem cells , as an alternative to chemotherapy in cancer patients. We synthesized various gold nanoparticles through microbial sources and assessed them using AFM, SEM
More importantly the scope of gold nanoparticles in ablation of breast cancer cells will be presented along with the important criteria developed in assessing feasibility of using them in future cancer therapeutics.
Liqun XiaAssistant research fellow
Sir Run Run Shaw Hospital, China
The N6-methyladenosine (m6A) has been recognized as the most prevalent and best-characterized mRNA modification currently. Accumulating evidences suggest that m6A regulates processes including self-renewal, differentiation, proliferation and apoptosis. The function and mechanism dissection of m6A in tumorgenesis and development has become a hot topic. We found that the m6A was decreased significantly in the clear cell renal cell carcinoma (ccRCC) tissues compared to the para-carcinoma tissues. RT-PCR analyses of 50 paired ccRCC and para-carcinoma tissues revealed that the RNA methytransferase METTL14 was dramatically reduced in the ccRCC (p<0.05). Consistently, the reduction of METTL14 protein in ccRCC was further confirmed by immunohistochemistry and western blot. ccRCC data from the TCGA also demonstrated a reduction of METTL14 in ccRCC. Moreover, the level of METTL14 is negatively related to the malignant degree and prognosis of ccRCC. Next, we altered the expression of METTL14 in ccRCC cell lines to explore the potential role of METTL14 in ccRCC. The result from CCK-8 assay showed no significant influence of METTL14 on cell growth. Results from wound healing, transwell migration and invasion assay demonstrated that knocking down METTL14 promoted ccRCC cell migration and invasion while overexpression of METTL14 repressed cell migration and invasion, indicating a protective role of METTL14 in ccRCC. Finally, we established the orthotopic mouse model of ccRCC with differed METTL14 level, and more metastases were observed in the shMETTL14 group. Further study is in progress to uncover the underlying mechanism how METTL14 regulate cell migration and invasion.
Abhimanyu MohantaAssociate Professor
Biju Pattnaik College, India
Objective: The objective of the study is to reveal the rare occurrence of cytological atypia appear to be an anuran tadpole larva, named as keratinized tadpole cell (KTC) in human oral tadpole cell carcinoma.
Materials and Methods: In a case- control study, a total of 272 subjects (136 oral cancer cases and 136 Control) were included. Exfoliated scraped cytosmears were collected from the affected sites of the clinically diagnosed 136 oral cancer patients over the pre-cleaned microslides and immediately fixed in acetoalcohol. Cytosmears were stained with routine Papanicolaou’s stain and counterstained with the Giemsa’s solution. Out of one thousand cells, the KTCs were scored from each stained sample following standard criteria. Findings were statistically analyzed, interpreted and correlated with the oral sites, sex and nature of addiction. Cytomorphometry and photomicrography was done by using computer assisted Bio-Catalyst Cat Cam 1.30 microscope camera.
Results: Rare occurrence of Keratinized tadpole cells (KTCs) exhibit both cytological and nuclear pleomorphism. Almost all KTCs are moderately differentiated with a well defined head and tail in each. Usually, nucleus is confined to the head part of the cell and tail contains cytoplasm only. Keratinized cytoplasm, nuclear pleomorphism, presence of nuclear haloes, micronucleation, multinucleation and increased nuclear-cytoplasmic ratios (N/C) in keratinized tadpole cells are the clear indication of malignancy so far as cytopathology is concerned.
Conclusion: Due to rare occurrence of KTCs in the human oral epithelia of clinically diagnosed cancer cases, it is to be considered as human oral tadpole cell carcinoma. From the cytodiagnostic point of view, it has also a practical utility in early detection and diagnosis of human oral carcinoma.
Pushpam Kumar SinhaResearcher
In my talk I consider cancers of those tissues that have adult stem cells in their lineage, and show that they have a common origin. Recently, it has been shown that most of the cancers have stem cell basis. To be more precise the blast cells of the cancer arise from cancer stem cells (CSCs) which possess most of the properties of corresponding adult stem cells (ASCs), like they are rare, quiet and can self-renew. Self-renewal of ASC means that the ASCs can undergo either asymmetric cell division to give rise to a daughter cell which is exact copy of mother cell and a partially differentiated progeny called the progenitor or symmetric cell division to give rise to two daughter cells which are exact copies of the mother cells. In a healthy tissue, the progenitor undergoes further cell division to yield terminally differentiated cells having specific morphologies and functions. In a healthy tissue there is a delicate balance between rates of self-renewal, apoptosis and differentiation to achieve homeostasis, i.e. steady state. The multiple mutations in ASCs or progenitor cells which disturb the balance between self-renewal, apoptosis and differentiation lead to cancer. These multiply mutated ASCs or progenitors are known as CSCs. Little is known about exactly what happens immediately after the multiple mutations leading to cancer have set in ASCs or progenitors. Through my work or this talk, I show that as a result of these multiple mutations the CSCs begin to both proliferate and undergo apoptosis aggressively. It is the large scale of apoptosis of highly mutated CSC that fools the homeostasis of organism. This is the genesis of cancer (i.e. fooling of homeostasis by CSCs) common to all cancers. Because the highly mutated CSCs are undergoing apoptosis in large numbers the repair mechanism of these cells are triggered to take corrective action by up-regulating the glucose metabolism pathway, and these cells thereby evolve into strong cells which do not further undergo apoptosis. Now we have only a bunch of highly proliferating mutated stem cells and cancer sets in. Based on my model of the origin of cancer I suggest two chemicals that can cure any type of cancer- Ethanol Alcohol Dehydrogenase and Sodium Meta bisulphite.
Sankha BhattacharyaAssociate professor
SVKM'S NMIMS Deemed-to-be University, India
The main objective of this research was to develop chitosan based polymeric nanoparticles of Imatinib (IMT-PNPs) for colorectal cancer targeting. The ionic gelation technique and central composite design was implemented to prepare IMT-PNPs. Out of 21 batches, F10 formulation was found to be optimized. The F10 was further evaluated for surface morphology, in-vitro drug release and release kinetic study, in-vitro drug deposition study, histopathological study, colon tissue uptake study using fluorescence microscopy, in-vitro cytotoxicity study & stability studies. The optimized formulations were found to have 208±0.01nm particle size, -32.56±0.03mV of zeta potential, 86.45±0.05% in-vitro cumulative drug release & 68.52±0.01% drug entrapment efficacy. Florescence study indicates, epithelial colon cells parade higher fluorescent nanoparticle accumulation after i.v. administration. The IMT-PNPs formulations show only 0.46% hemolysis, which indicates the formulation is safer for i.v. administraction. In histopathological evaluation, the final formulations show no sign of damage in tissues, which indicates the final formulation can be safely administered through i.v route. From the MTT assay, it can be witnessed that encapsulated IMT-PNPs produces higher & controlled cytotoxicity in CT26 colon carcinoma cell lines. The outcomes of this research confined, IMT-PNPs could be an effective approach in colorectal cancer targeting using i.v. route.
Ajit Kumar kushwahaAssistant professor
Objective: reconstruction after resection of head and neck cancer has always been challenging effort. In this study we have described the usefulness of suprascapular flap in head and neck oncological defect Method: all head and neck cancer patients who underwent pedicled suprascapular flap from August 2019 to march 2020 at RIMS, Ranchi were included in the study retrospectively. The outcome and complications associated with suprascapular flap reconstruction were evaluated. Results: a total of 7 patients underwent pedicled suprascapular flap reconstruction during the period. Three were female and four male. Mean size of defect was 5.2 X 4.2 cm. Average duration for flap harvesting was 37min and mean blood loss was 31ml. Donor site was closed primarily in six patients, one required split thickness graft. There were no donor site related complications. There was partial flap loss in two patient. Conclusion: suprascapular flap is easy to harvest and offers a good alternative to free flap in head and neck oncological reconstruction.
Instability and dynamic self-organization of the cancer cell system. The hypothesis of the cancerogenic hypercycle
Malzev Vladimir NDoctor-urologist
Hannover Medical School, Germany
The mechanism that is the base of all hallmarks is the genetic instability as a result of continuously occurring mutations and egipenomic DNA modifications in a cancer cell. It cannot be explained by simple accumulation of genome mutations. Continuous mutation and epigenetic modification are only possible as a result of continuous impact of a mutagenic factor. Cyclic DNA replication reaction and/or RNA of mobile genetic elements are this
mutagenic agent. These elements are generated as a result of inner-cell chaos of molecular biological processes that is caused by the impact of a cancerogenic factor. After their generation, they can create a hypercyclic link to the cell DNA replication cycle and hence cause mutations and epigenetic modifications in this cell. A new type of selforganisation of inner-cell processes and structures named primary cancerogenic hypercycle is generated. These changes progress, but remain hidden until they affect certain weak points of the cell genome. As a result, additional cyclic processes are generated that support the primary cancerogenic hypercycle and entail the generation of a second-order hypercycle. Hypercycles of the second order and over are hallmarks of cancer, and they ensure a competitive advantage with regard to the cyclic DNA replication reaction of environmental healthy cells. Since this
moment, a pre-cancer cell becomes a cancerous one. The primary cancerogenic hypercycle remains a homogenous structure during the whole cancerogenesis. This hypothesis reveals new principles of cancer treatment that are presented on this poster.
Rama Rao MallaProfessor
Triple negative breast cancer (TNBC) is aggressive and negative hormone receptors. Approximately 1/3 of paclitaxel resistant breast cancers are triple negative. Silencing of CD151 with small molecular inhibitor 2-thio-6-azauridine (TAU), inhibited proliferation of TNBC cells. In this context, designing of feasible therapeutic options by combining targeted therapy with radiation therapy may kill more tumour cells. In the current study paclitaxel-resistant triple negative breast cancer cell lines (PtxR/TNBC) were developed using intermittent step-wise treatment. Further, effect of radiation on TAU induced apoptosis and CD151 mediated drug resistance mechanism was be studied and elucidated. In the current webinar, CD151 mediated drug resistance mechanism in tripe negative breast cancer will be presented and discussed.
Neferine and isoliensinine enhance ‘intracellular uptake of cisplatin’ and induce ‘ROS-mediated apoptosis’ in colorectal cancer cells – a comparative study
V.Vijaya PadmaProfessor & Head
Bharathiar University, India
Cisplatin (CDDP) is a potent platinum-based chemotherapeutic agent used to treat solid tumors including colorectal cancer by inducing cytotoxicity through DNA damage and DNA synthesis inhibition. However, CDDP usage is limited due to the chemoresistance and associated adverse effects. A combinatorial regimen of dietary phytochemical components seems to be a hopeful strategy for future drug development. Lotus-derived compounds such as neferine and isoliensinine have proven significant chemosensitizing activity in different cancer cells. The present study aims to compare the chemosensitizing activity/anticancer potential of neferine/isoliensinine in combinatorial regimen with CDDP. Our results documented that neferine/isoliensinine in combination with CDDP augmented ‘intracellular uptake of cisplatin’ and consequent apoptosis in HCT-15 cells exemplified by the ‘apoptotic morphological changes’, ‘S phase cell cycle arrest’, ‘ROS mediated oxidative stress’ with concomitant escalation in intracellular calcium [Ca2+] & dissipation of mitochondrial membrane potential (ΔψM) and activation of MAPK/PI3K/AKT pathway’. Furthermore, isoliensinine combinatorial regimen with CDDP exclusively enhanced CDDP uptake and induced more ROS-mediated apoptosis compared to neferine + CDDP, neferine, isoliensinine, IC50 of CDDP alone. Western blot analysis depicted that the combination regimens induced downregulation of Bcl2, PI3K, pAKT and upregulation of cytochrome c, caspase 3, 9, PARP cleavage & p38 and pP38. Results suggested that CDDP combination with neferine/isoliensinine augment the anticancer potential of CDDP in an additive manner and decrease the CDDP dose requirement.
The importance of treating energy imbalances and Chakras replenishment for prevention and treatment of Cancer
Wei Ling HuangAcupuncturist
Medical acupuncture and Pain Management Clinic, Brasil
Western medicine’s cancer treatment focus on the destruction of the diseased cells. In traditional Chinese medicine (TCM), cancer is the manifestation of the body’s energy deficiency and Heat retention. Purpose: To demonstrate that cancer patients have energy deficiencies and Heat retention as root and also chakra’s energy deficiencies in the lowest level. The balance of the energy deficiencies and taking out the Heat retention associated with the replenishment of these energies is important to prevent and treat cancer patients. Methods: Three clinical cases reports. All three patients with cancer diagnoses (case one: thyroid; case two: uterus; case three: lungs). All of them received treatment to reestablish the equilibrium between Yin, Yang, Qi, Blood and taking out Heat retention through Chinese dietary counselling, auricular acupuncture with apex-ear bloodletting, homeopathy according to the Constitutional Homeopathy of Five Elements Based on Traditional Chinese Medicine and crystal-based medication after chakras energy measurement through radiesthesia procedure. All three patients were found to be at their lowest level of energy, rating one out of eight. Results: Out of the three patients, the first two case reports were cured of their cancer condition without any treatment by Western medicine, only with the treatment done. The third patient, though, was already under radiotherapy and chemotherapy but through the treatment previously described the metastasis disappeared and he achieved a better physical and emotional health state. Conclusion: TCM believes that energy deficiency and Heat retention causes cancer. Treatment with Chinese dietary counseling, auricular acupuncture, apex-ear bloodletting and recharge of the chakras energy can be a path to prevention and treatment of cancer patients.
Michael J GonzalezProfessor
University of Puerto Rico Medical Sciences Campus, USA
The altered energy metabolism of tumor cells provides a viable target for a non toxic chemotherapeutic approach. An increased glucose consumption rate has been observed in malignant cells. Warburg (Nobel Laureate in medicine) postulated that the respiratory process of malignant cells was impaired and that the transformation of a normal cell to malignant was due to defects in the aerobic respiratory pathways. Szent-Gyorgyi (Nobel Laureate in medicine) also viewed cancer as originating from insufficient availability of oxygen. Oxygen by itself has an inhibitory action on malignant cell proliferation by interfering with anaerobic respiration (fermentation and lactic acid production). Interestingly, during cell differentiation (where cell energy level is high) there is an increased cellular production of oxidants that appear to provide one type of physiological stimulation for changes in gene expression that may lead to a terminal differentiated state. The failure to maintain high ATP production (high cell energy levels) may be a consequence of inactivation of key enzymes, especially those related to the Krebs cycle and the electron transport system. A distorted mitochondrial function (transmembrane potential) may result. This aspect could be suggestive of an important mitochondrial involvement in the carcinogenic process in addition to presenting it as a possible therapeutic target for cancer. Intermediate metabolic correction of the mitochondria is postulated as a possible non-toxic therapeutic approach for cancer.
Repurposing Mefloquine an Antimalarial drug as an adjuvant in Cisplatin mediated anticancer activity
Jyotirmoi AichAssistant Professor
D Y Patil Deemed to be University, India
Cancer is one of the deadliest diseases that has been the major cause of deaths for the last few decades, second in line with Cardiac disorders. With increasing incidences of resistance to chemotherapy it is difficult to come up with novel anticancer drugs. One approach to combat this resistance is drug repurposing. Anticancer drug development is a tedious process, requiring a number of in-vitro, in-vivo and clinical studies. Drug repurposing approach for this process, brings down the time money and resources needed. The use of computational tools, to find new indications for drugs with well-established profiles before conducing wet lab experiments increases the possibility of positive outcome. Mefloquine, one of the most potent quinine analogues have been selected as a candidate to evaluate its anticancer properties and potential use in combination therapy along with cisplatin, a well characterized clinically accepted anticancer drug. The drug repurposing potential of mefloquine as adjuvant chemotherapy in cancer was delineated using various in-silico and in-vitro studies. Knowledge based and text mining drug repurposing approach was used. Molecular docking was performed for various genes which have been shown to play crucial role in cancer pathophysiology. Cytotoxicity studies of Mefloquine and cisplatin in MCF-7, a breast cancer cell line alone and in combination revealed some non-synergistic combinations which can be used for reducing the toxicity of Cisplatin chemotherapy. Our study identified the drug repurposing potential of mefloquine so that it can be used as an adjuvant in cisplatin mediated chemotherapy.
Jianhua LuoProfessor, USA
University of Pittsburgh School of Medicine, USA
Chromosome mutations and rearrangements are some of the hallmarks of human malignancies. Chromosomal rearrangement is frequent in human cancers. One of the consequences of chromosomal rearrangement is gene fusions in the cancer genome. We have identified a panel of fusion genes in aggressive prostate cancers. In the present study, we found that these fusion genes are present in 7 different types of human malignancies with variable frequencies. Among them, CCNH-C5orf30 and TRMT11-GRIK2 gene fusions were found in breast cancer, colon cancer, non-small cell lung cancer, esophageal adenocarcinoma, glioblastoma multiforme, ovarian cancer and liver cancer, with frequencies ranging from 12.9% to 85%. In contrast, four other gene fusions (mTOR-TP53BP1, TMEM135-CCDC67, KDM4-AC011523.2 and LRRC59-FLJ60017) are less frequent. Both TRMT11-GRIK2 and CCNH-C5orf30 are also frequently present in lymph node metastatic cancer samples from the breast, colon and ovary. Some of these fusion transcripts are present in the peripheral blood of cancer patients, making these fusion genes important blood markers for human malignancies. One of these fusion genes called MAN2A1-FER generates a constitutively activated tyrosine protein kinase. The fusion protein translocates the FER kinase domain from the cytoplasm to Golgi apparatus, and ectopically phosphorylates the extracellular domains of several growth factor receptors including EGFR, and activates multiple pro-growth signaling pathways in the absence of ligands. MAN2A1-FER has been found in a variety of human malignancies. It transforms immortalized cell lines into highly aggressive cancer cells. Expression of MAN2A1-FER produces spontaneous liver cancer in animals. Cancer cells positive for MAN2A1-FER are highly sensitive to several tyrosine kinase inhibitors, and can be targeted by genome and immune therapy intervention. Thus, targeting at MAN2A1-FER or other oncogenic fusion genes may hold promise to treat human cancers effectively.
Gastric cancer personalised precision surgery and sentinel node directed minimally invasive resections; an appraisal
Viswanath YKSProfessor of Surgery
Teesside University, UK
Prior accurate pre-intervention staging assessments are necessary for management of early oesophageal cancer (squamous cell and adenocarcinoma). At present, endoscopy, CT scan, CT PET scan and EUS are 4 pillars, enabling the multidisciplinary team to elect appropriate evidence based treatment modality. The decision is taken based on cancer patient fitness, willingness and staging. For operable cancer with lymph node involvement, one needs to consider systemic therapy based on neo-adjuvant chemotherapy, including those with early / localized oesophageal cancer. This formal presentation, aims at examining role of endoscopic ultrasound scan (EUS) and Computerised Tomography Positron Emissions Tomography (CT PET) in identifying right patients for endoscopic and surgical therapy. This accompanied by a brief discussion of cancer survival along with upcoming staging gizmos and their potential impact in future years.
Small cell neuroendocrine carcinoma of the urinary bladder: A clinicopathologic and immunohistochemical study for improving patient selection to clinical trials
Alessandro D'AmuriSurgical Pathologist
Unit "A. Perrino" Hospital, Italy
Small cell carcinoma (SmCC) of the urinary bladder is a rare, aggressive, poorly differentiated neuroendocrine neoplasm accounting for 0,3-0,7% of bladder tumours. Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma, a better understanding of SmCC could be achieved to provide solid evidence for clinicopathology and prognosis. Few protocols encounter small cell neuroendocrine carcinoma with detailed clinico-pathological features among clinical trials. We reviewed the parameters visuable at morphology among a series of small cell carcinoma arising from urothelium. We retrospectively studied a large series of bladder SmCC from a single Institution. The patients included 25 men and 10 women. The ages of onset ranged from 63 to 90, with the median age being 78. All bladder SmCC were presented at advanced stage with tumors invading the muscularis propria and beyond (n=35). SmCC was pure in 30 cases and mixed with other histologic types in 5 cases, including urothelial carcinoma (UC) (n=3), UC in situ (n=1), and squamous (n=1) features. Compared to conventional UC at similar stages, SmCC had a worse prognosis only when patients developed metastatic diseases. Small cell carcinoma of the bladder occurs more often in elderly males and prognosis is poor; tumor cells are strongly positive for CKAE1/AE3, CAM 5.2, p53 and focally for CK34B12, CK7, CK20, TTF-1, c-Kit and p63. Most cases are immunoreactive for neuroendocrine markers such as diffusely for CD56, NSE and focally for synaptophysin and chromogranin. Recognition of this rare entity should enable better detailed tumour clustering when designing clinical trials using drugs targeting patient affected by small cell neurondocrine phenotype of urothelial carcinoma.
Polyploidization is a strong driving force towards increasing genomic instability that occurs twice during two critical events during tumor progression first due to an evolutionary conserved phenomeno
Roland SennerstamAssociate professor
Karolinska Hospital and Karolinska Institute, Sweden
Tetraploidization occurs twice in growing breast tumor cells. Initially very early in tumor progression as a reflection of a common phenomenon reported during cleavages of the evolution tree and in human body tissues gaining hardware in a response to various stress factors as lactating breasts, lever virus infection, Hashimoto thyroid infection, in placenta and in overloaded left heart ventricle e.tc. Having a model for increasing genomic instability we can follow the steps of polyploidizations using young women with breast cancer < 40 years of age. Already at a low level of genomic instability the tumor cells appear as DNA diploid and tetraploid population. Mainly due to mitotic failure the tetraploid cells lose genetic materials and appear with cells in the hypo-tetraploid and aneuploid triploid tumor DNA areas. During these alterations the tumors increase in size and reach a state of suffering from nourishment and oxygen, due to lack of blood vessel penetration. This stress situation force tumor cells to another polyploidization among both diploid and aneuploid cells. The last group will double their genome to appear in the penta- to octa-ploidy DNA region. The degree of malignancy potential increases due to the stepwise genomic instability and the most rapid death rate occurs among breast cancers in the penta- to octa-ploidy DNA tumors. Tumors remaining as diploid have as the best survival time during 15 years of follow up as confirmed in many studies.
Clinical trial evaluating the efficacy of cell therapy for the treatment of chronic radiotherapyinduced abdomino-pelvic complications
The late adverse effects of pelvic radiotherapy concern 5 to 10% of patients, which could be life threatening. However, a clear medical consensus concerning the clinical management of such healthy tissue sequelae does not exist. Our group has demonstrated in preclinical animal models that systemic mesenchymal stromal stem cells (MSCs) injection is a promising approach for the medical management of gastrointestinal disorder after irradiation.
In a phase 1 clinical trial, we have shown that the clinical status of four first patients suffering from severe pelvic side effects (Epinal accident) was improved following MSC injection (figure). Two patients revealed a substantiated clinical response for pain and hemorrhage after MSC therapy. The frequency of painful diarrhea diminished from 6/d to 3/d after the first and 2/d after the 2nd MSC injection in one patient. A beginning fistulization process could be stopped in one patient resulting in a stable remission for more than 3 years of follow-up. A modulation of the lymphocyte subsets towards a regulatory pattern and diminution of activated T cells accompanies the clinical response. MSC therapy was effective on pain, diarrhea, hemorrhage, inflammation, fibrosis and limited fistulization. No toxicity was observed.
We are now starting a clinical research protocol for patients with post-radiation abdominal and pelvic complications who have not seen their symptoms improve after conventional treatments (NCT02814864, Trial evaluating the efficacy of systemic MSC injections for the treatment of severe and chronic radiotherapy-induced abdomino-pelvic complications refractory to standard therapy (PRISME). It involves the participation of 6 radiotherapy services for the recruitment of 12 patients. They will all be treated and followed up in the hematology department of Saint Antoine Hospital. The cells will be prepared in two production centers (EFS Mondor and CTSA). Treatment is a suspension of allogeneic MSCs. Eligible patients must have a grade greater than 2 for rectoragy or hematuria at inclusion and absence of active cancer. Each patient receives 3 injections of MSCs at 7-day intervals. Patients will be followed up over a 12-month period. The main objective is a decrease of one grade on the LENT SOMA scale for rectorrhagia or hematuria. The secondary objective is to reduce the frequency of diarrhea; analgesic consumption, pain and improved quality of life.
Characterisation of proto-oncogenic anterior gradient protein 2 (AGR2) interactome in patients with esophageal adenocarcinoma (EA) and its potential implication on new cancer remedial targets
Viswanath YKSProfessor of Surgery
Teesside University, UK
Amongst a few cancers, enhanced AGR2 proteins expression is associated with cancer invasion, survival, chemotherapy resistance and tumour growth. Overexpression of AGR2 was been reported to correlate with metastasis and poor prognosis in breast cancer and considered as a biomarker in prostate cancer. Esophageal adenocarcinoma is more prevalent in Western Europe and associated with poor 5 year survival (14-18%). Although AGRS-2 is expressed in esophageal adenocarcinoma (EA), its molecular interactions (interactome) and their co-expression is not fully understood. This presentation covers original research discussing comportment of AGR2 proteins when analyzed under oxidizing conditions and discuss identification of novel interacting proteins by way of alkylation trapping and immunoprecipitation approach. The carried out innovative research demonstrate AGR2 protein preferential engagement with MUC-5AC (mucin-5AC) which is co-expressed in patients with EGA and a potential new therapeutic cancer target. This research untangles new potential therapeutics targets in the management of EA.
Meheangiz ZamaniAssociate Professor
Hamedan University of Medical Sciences, Iran
Aggressive angiomyxoma is an uncommon mesenchymal tumor in women who are in reproductive age, that occurring in the pelvis and perineal zone with a high risk of local infiltration and recurrence. Surgery is the first line and best treatment; however some adjuvant treatments, such as Decapeptide, may be effective against tumor recurrence .We describe a case of a 28-year-old woman with a huge recurrent vulvar aggressive angiomyxoma