Chemotherapeutic Management Research Articles

Anti-Tuberculosis Potential of OJT008 against Active and Multi-Drug-Resistant Mycobacterium Tuberculosis: In Silico and In Vitro Inhibition of Methionine Aminopeptidase.

Despite the recent progress in the diagnosis of tuberculosis (TB), the chemotherapeutic management of TB continues to be challenging. Mycobacterium tuberculosis (Mtb), the etiological agent of TB, is classified as the 13th leading cause of death globally. In addition, 450,000 people were reported to develop multi-drug-resistant TB globally. The current project focuses on targeting methionine aminopeptidase (MetAP), an essential protein for the viability of Mtb. MetAP is a metalloprotease that catalyzes the excision of the N-terminal methionine (NME) during protein synthesis, allowing the enzyme to be an auspicious target for the development of novel therapeutic agents for the treatment of TB. Mtb possesses two MetAP1 isoforms, MtMetAP1a and MtMetAP1c, which are vital for Mtb viability and, hence, a promising chemotherapeutic target for Mtb therapy. In this study, we cloned and overexpressed recombinant MtMetAP1c. We investigated the in vitro inhibitory effect of the novel MetAP inhibitor, OJT008, on the cobalt ion- and nickel ion-activated MtMetAP1c, and the mechanism of action was elucidated through an in silico approach. The compound's potency against replicating and multi-drug-resistant (MDR) Mtb strains was also investigated. The induction of the overexpressed recombinant MtMetAP1c was optimized at 8 h with a final concentration of 1 mM Isopropyl β-D-1-thiogalactopyranoside. The average yield from 1 L of Escherichia coli culture for MtMetAP1c was 4.65 mg. A preliminary MtMetAP1c metal dependency screen showed optimum activation with nickel and cobalt ions occurred at 100 µM. The half-maximal inhibitory concentration (IC50) values of OJT008 against MtMetAP1c activated with CoCl2 and NiCl2 were 11 µM and 40 µM, respectively. The in silico study showed OJT008 strongly binds to both metal-activated MtMetAP1c, as evidenced by strong molecular interactions and a higher binding score, thereby corroborating our result. This in silico study validated the pharmacophore's metal specificity. The potency of OJT008 against both active and MDR Mtb was <0.063 µg/mL. Our study reports OJT008 as an inhibitor of MtMetAP1c, which is potent at low micromolar concentrations against both active susceptible and MDR Mtb. These results suggest OJT008 is a potential lead compound for the development of novel small molecules for the therapeutic management of TB.

Molecular profiling of pre- and post-treatment pediatric high-grade astrocytomas reveals acquired increased tumor mutation burden in a subset of recurrences

Diffuse gliomas are a heterogeneous category of primary central nervous system tumors. Due to their infiltrative growth precluding complete surgical resection, most diffuse high-grade gliomas are treated with adjuvant chemotherapy and radiation. Recurrent/progressive diffuse gliomas may show genetic differences when compared to the primary tumors, giving insight into their molecular evolution and mechanisms of treatment resistance. In adult-type diffuse gliomas with or without isocitrate dehydrogenase gene mutations, tumor recurrence/progression can be associated with mutations in genes encoding DNA mismatch repair proteins, leading to a dramatic increase in tumor mutation burden. This phenomenon is closely linked to treatment with the DNA alkylating agent temozolomide, a mainstay of adult diffuse glioma chemotherapeutic management. Post-treatment mismatch repair deficiency and acquired high tumor mutation burden is relatively unexplored in pediatric patients who have recurrent high-grade gliomas. Here, we report a molecular and histological analysis of an institutional cohort of eleven pediatric patients with paired initial and recurrent high-grade astrocytoma samples with intervening temozolomide treatment. We identified three cases with evidence for increased tumor mutation burden at recurrence, including two cases of diffuse hemispheric glioma H3 G34-mutant (one previously reported). We also show that molecular analysis by next-generation DNA sequencing and DNA methylation-based profiling enabled an integrated diagnosis per 2021 World Health Organization criteria in 10 of 11 cases (91%). Our findings indicate that increased tumor mutation burden at post-treatment recurrence is relevant in pediatric-type diffuse high-grade gliomas. Diffuse hemispheric glioma H3 G34-mutant may be particularly susceptible to this phenomenon.

MiR 378a/FSCN1 regulatory axis inhibits tumor stemness and increases the cytotoxicity of chemotherapeutic drugs in colorectal cancer cells

Purpose: To evaluate the effect of miR-378a/FSCN1 axis on tumor stemness and aerobic glycolysis in colorectal cancer cells (CRC).&#x0D; Methods: Abnormal expressions of miR-378a and FSCN1 in CRC tissues were analyzed through TCGA database. Cell viability and apoptosis were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay and flow cytometry, respectively, while expression of miR-378a was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Furthermore, Western blotting assay was used to assess protein expressions. The miR-378a target was evaluated using ENCORI and confirmed by luciferase assay. Aerobic glycolysis was evaluated by determining glucose uptake, lactate production and lactate dehydrogenase (LDH) activity.&#x0D; Results: Downregulation of miR-378a and upregulation of FSCN1 were observed in both CRC tissues and cell lines (p &lt; 0.05). Overexpression of miR-378a and repression of FSCN1 reduced cell viability and tumor sphere formation, and induced cell apoptosis. Protein expression of SOX2, KLF4, Bmi1 and Oct-4 were downregulated by either the overexpression of miR-378a or repression of FSCN1 (p &lt; 0.01). Glucose uptake, lactate production and LDH activity were inhibited by either overexpression of miR-378a or repression of FSCN1, while cytotoxicity of Dox and 5-Fu was increased by upregulation of miR-378a or downregulation of FSCN1 (p &lt; 0.05). The predictive results of ENCORI demonstrated that FSCN1 was the direct target of miR-378a, and this was confirmed by luciferase assay results (p &lt; 0.005). All the effects of miR-378a in CRC were reversed by overexpression of FSCN1 (p &lt; 0.05).&#x0D; Conclusion: This study has shown that miR-378a suppresses tumor stemness and increases the cytotoxicity of chemotherapeutic drugs by directly targeting FSCN1, resulting in the prevention of CRC tumorigenesis. Thus, these findings suggest a new approach to the chemotherapeutic management of CRC.

Effect of isolated grandivittin from Ferulago trifida Boiss. (Apiaceae) on the proliferation and apoptosis of human lung cancer A549 cells.

Lung cancer is one of the deadliest cancers in the world. Introducing new promising agents can help the chemotherapeutic management of cancer. In the knowledge of oncology, plants are of special interest as a rich source of new antineoplastic and chemotherapeutic agents. Grandivittin (GRA) is one of the main constituents of Ferulago trifida Boiss. with established medicinal, phytochemical, and pharmacological properties. This study aimed to isolate and evaluate the antineoplastic potential of grandivittin and its underlying mechanisms in human lung cancer A549 cells. The viability of the A549 cells after being treated with 0.1, 0.4, 0.7, 1, and 1.3mM of GRA for three following days was measured using the MTT method. The early apoptosis and late apoptosis were assessed by fluorescence-activated cell sorter analysis through annexin V/PI staining. The expression of apoptotic agents' genes (caspase 3, caspase 9, Bcl2, Bax, and P53) was evaluated by the RT-PCR method. GRA increased apoptotic cells and decreased cell viability in a dose- and time-dependent manner, in which only 50% of cells survived at a dose of 0.7mM. The expression of Bax, P53, caspase 3, and caspase 9 genes in the A549 cells was significantly upregulated after GRA treatment compared to control cells (P < 0.05). On the other hand, Bcl2 was significantly downregulated after GRA treatment (P < 0.05). The results indicated that GRA can activate cell death in A549 lung carcinoma cells by inducing both DNA toxicity p53 and cascade-dependent pathways. Therefore, GRA may be a potential new therapeutic agent for the treatment of lung cancer.

Profile of HER2/neu Expression in Surface Epithelial Ovarian Tumours: A Clinicomorphological Study

Introduction: Surface Epithelial Ovarian Tumours (SEOT) are most prevalent tumours and account for about two third of all ovarian cancers. Survival of ovarian carcinoma is poor despite optimal surgical and chemotherapeutic management. Evaluation of new diagnostic and prognostic Immunohistochemical (IHC) markers will be essential in this aspect. Aim: To evaluate quantitatively the profile of Human Epidermal growth factor Receptor 2 (HER2)/neu IHC expression with standard scoring system in SEOTs and their association with various clinicpathologic variables (age, laterality, CA 125 levels, histological subtype and FIGO staging). Materials and Methods: The present ambispective study was done in the Department of Pathology, SRM Medical College Hospital and Research Centre, Kattankulathur, Tamil Nadu, India, from August 2020 to August 2022 with a sample size of 166 cases. All the histopathological samples of SEOT during the study period from August 2020 to August 2022 (prospective) and all borderline, malignant and few benign cases from June 2016 to August 2020 (retrospective) were also included in the study. Cases for which slides and blocks were not available and patient treated with neo adjuvant chemotherapy or radiotherapy were excluded in the study. For prospective cases after getting clinical history and Cancer Antigen 125 (CA 125) level, specimens were fixed, processed and Haematoxylin and Eosin (H&amp;E), IHC staining was done as per standard lab protocol, for retrospective cases clinical history, CA 125 levels, pathological diagnosis and tissue blocks were retrieved, IHC performed and finally both prospective and retrospective cases HER2/neu IHC expression association was studied related to clinicopathological parameters. Results: Out of total sample, SEOT was the most common (n=184, 76.98%) tumour cases, followed by germ cell tumours (n=42, 17.57%) cases and least common was sex cord stromal tumour (n=13, 5.43%). HER2/neu had higher IHC expression in malignant tumours and showed statistically significant positive association with age (p-value=0.001), CA 125 level (p-value0.001), and histological diagnosis (p-value &lt;0.001), but there is no significant association with size of tumour (p-value=0.786), parity (p-value=0.717), laterality (p-value=0.514) and the International Federation of Gynecology and Obstetrics (FIGO) grading (p-value=0.274). Conclusion: Malignant tumours had high HER2/neu IHC expression, thus emphasising its carcinogenic role and helps in the diagnostic differentiation of benign and borderline tumours with malignant potential from actual malignant tumours and can be a therapeutic target in future.

Impact of COVID-19 Pandemic on the Utilisation of Medical Oncology Services at a Tertiary Care Hospital in Srinagar, India: A Retrospective Study

Introduction: Coronavirus Disease-19 (COVID-19) Pandemic affected healthcare delivery worldwide from all quarters be it routine or essential care, including cancer care. All aspects like screening, diagnosis, and treatment were affected regardless of the developmental status of countries. Aim: To find out the extent and magnitude of cancer care affected during pandemic by comparing the data during pandemic for outpatient visits, new registrations, admissions, and day-care chemotherapy sessions with prepandemic data. Materials and Methods: This retrospective study was conducted in the Department of Medical Oncology of State Cancer Institute in Srinagar, India. The parameters assessed were the number of outpatient visits, new registrations, admissions, and day care chemotherapy sessions from the department of Medical Oncology. Anonymised cumulative data of all the patients who availed these services was included. Data were collected for eight months, during pandemic in 2020 and were compared with the data from previous year 2019. The effect of lockdown was assessed by comparing these parameters with the non lockdown period. Statistical analysis was done by independent t-test. Results: The number of outpatient visits dropped from 15425 from non lockdown period to 12670 in lockdown period (p-value=0.019), number of new admissions from 1613 to 1418 (p-value=0.001), and chemotherapy sessions from 9374 to 8081, (p-value=0.004). The number of patient registrations also declined but the drop was not significant (p-value=0.171). All the parameters except in-patient admission improved during the non lockdown period with the highest improvement in registration, but inpatient admission revealed a similar reduction as in the lockdown period. Conclusion: There was a significant effect of lock down due to COVID-19 pandemic on the number of outpatient visits, new admissions and chemotherapy sessions. This infers that, the treatment protocols and chemotherapeutic management of cancer care were badly affected by the advent of the pandemic.

8665 Minimally Invasive Surgical Management of Placental Site Trophoblastic Tumor

<h3>Study Objective</h3> We present a unique case of presumed stage 1 placental site trophoblastic tumor (PSTT) with an incidental pancreatic mass noted on MRI. A minimally invasive surgical approach was planned in combination between gynecologic oncology and surgical oncology. <h3>Design</h3> Single patient case report. <h3>Setting</h3> Academic quaternary care hospital. <h3>Patients or Participants</h3> A 31-year-old G4P0131 was diagnosed with PSTT four months following a spontaneous abortion. Her preoperative evaluation included a β-hCG which plateaued at 80 milliunits/mL, magnetic resonance imaging with a 2 cm mass in the body of the pancreas, and no other evidence of metastatic disease. The pancreatic mass had imaging characteristics suggestive of a pseudopapillary neoplasm of the pancreas. Patient declined preoperative upper endoscopic ultrasound with biopsy. Due to the presumed low malignant potential of the pancreatic lesion and low likelihood of metastatic disease to the pancreas, she was deemed low-risk with a WHO score of 3. She had completed childbearing and surgical management with hysterectomy was recommended. <h3>Interventions</h3> A combined robotic assisted total laparoscopic hysterectomy and laparoscopic distal pancreatectomy and splenectomy. <h3>Measurements and Main Results</h3> The patient was discharged home on postoperative day three after the above procedure and had an uncomplicated postoperative course. Final pathology revealed a metastatic implant in the pancreas. The patient has since completed adjuvant chemotherapy with EMA/CO. β-hCG down trended to within normal limits and the patient currently has no evidence of disease. <h3>Conclusion</h3> We present a case of a rare tumor with an unusual metastatic pattern. Given its rarity, minimally invasive surgical management should remain the standard for low risk PSTT. However, preoperative biopsy could be beneficial with unusual imaging findings as high risk PSTT requires chemotherapeutic management.

Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers

Simple summaryLow-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III–IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved.BackgroundLow-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence.MethodsWe retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan–Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula.ResultsA total of 92 patients were included (median age was 47 years, IQR 35–64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1–10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1–10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1–10 mm (HR = 2.30, 95% CI 1.30–4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92–7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52–6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS.ConclusionsOptimal cytoreductive surgery improves survival outcomes in advanced stage LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

Chemotherapeutic Drugs Induced Symptom Distress Among Pediatric Cancer Patients

Pediatric cancer treatment includes several chemotherapeutic drugs in combination with adequate supportive management. Symptom distress among pediatric cancer patients on chemotherapy interferes with treatment compliance. Poorly managed distress leads to the decline of the child’s ability physically and mentally and deteriorates the quality of life. This paper shows the effect of chemotherapeutic drugs induced symptom distress, and the effect of early diagnosis in the management and improvement in the quality of life of pediatric cancer patients. For this study60, pediatric cancer patients aged between 10 to 18 years including both the gender were chosen using purposive sampling. Using the M.D. Anderson symptom inventory the symptom distress experienced by the pediatric cancer patients was assessed. The present quantitative cross-sectional study was conducted at the AIIMS, Raipur. The data were analyzed using the descriptive Statistical Package for Social Science Version 16 (SPSS 16). The categorical data was analyzed using chi –square test and the cut off p-value at ≤0.05. Among, the pediatric cancer patients 77.65% (SD 18.85) were experiencing severe symptom distress when on chemotherapy. Whereas 53.65 %( SD 9.63). of them experiencing the symptoms those disturb their activities of daily living in the last twenty four hours at p-value of ≤0.05. There is a need for an adequate support system from the school, social relationship, siblings, and health care team for improving the quality of life of pediatric cancer patients. Animal facilitated therapy, artistics expressions, medical play, procedural education, well organized home bound or school programs help the pediatric cancer patients to manage the symptom distress, thereby improving the treatment outcome. The specific supportive chemotherapeutic management is essential for the pediatric cancer patient’s treatment compliance and prognosis. The health care team, especially nurses play a vital role in early detection of chemotherapeutic agents induced symptom distress and its management.

Plant-Derived Natural Products as Lead Agents against Common Respiratory Diseases.

Never has the world been more challenged by respiratory diseases (RDs) than it has witnessed in the last few decades. This is evident in the plethora of acute and chronic respiratory conditions, ranging from asthma and chronic obstructive pulmonary disease (COPD) to multidrug-resistant tuberculosis, pneumonia, influenza, and more recently, the novel coronavirus (COVID-19) disease. Unfortunately, the emergence of drug-resistant strains of pathogens, drug toxicity and side effects are drawbacks to effective chemotherapeutic management of RDs; hence, our focus on natural sources because of their unique chemical diversities and novel therapeutic applications. This review provides a summary on some common RDs, their management strategies, and the prospect of plant-derived natural products in the search for new drugs against common respiratory diseases.

Antibiotics Sensitivity of Escherichia coli to Different Concentrations of Combined Herbal Drugs

Background: The use of combinational approach in chemotherapeutic management has proven more effective against infectious disease and lower resistance development but the untoward effect of this is yet to be explored for alternative medicine.&#x0D; Aims: This study aimed to study the effect of a combinational approach of herbal drugs on Escherichia coli response.&#x0D; Methods: E. coli was treated in different concentrations of combined herbal drugs (Beta herbal drugs and Deep root herbal mixture – BD) and (Beta herbal drug and Goko cleanser – BG). The different concentrations of the mixtures employed were: 33.3%, 11.1%, 3.7%, 1.2% and 0.4%. The bacteria concentration of 103 CFU/ml was treated in the different concentrations of the herbal drugs. The growth response of the cultures were analyzed at 24 and 48 hrs. The antibiotic sensitivity of the bacteria exposed to the herbal drugs were measured against perfloxacin (PEF), ciprofloxacin (CIP), streptomycin (S), and septrin (SEP).&#x0D; Results: The growth response curve showed growth of E. coli peaked in the lower concentrations but levelled down in the higher concentrations. 24 hr growth conditions showed much higher growth level than 48 hr. Higher concentrations of BG drug combination showed higher zones of clearance and only one concentration showed resistance: 0.4% (CIP). There was no unique pattern seen in the sensitivity of E. coli treated with BD however, there was five (5) cases of complete resistance: 0.4% (PEF), 1.2% (PEF) and 11.1% (CIP and SEP).&#x0D; Conclusion: In vitro, the combined herbal drugs do not completely eliminate E. coli. However, some concentrations of the combinations demonstrated complete resistance to the antibiotics which shows that these locally made antimicrobial could confer antibiotic resistance to E. coli.

American Gastroenterological Association Institute and College of American Pathologists Quality Measure Development for Detection of Mismatch Repair Deficiency and Lynch Syndrome Management

American Gastroenterological Association Institute and College of American Pathologists Quality Measure Development for Detection of Mismatch Repair Deficiency and Lynch Syndrome Management

Clinical management of pediatric chordomas: a comprehensive review.

Chordomas are malignant tumors derived from remnants of the notochord. These are extremely rare in pediatric patients, accounting for approximately 5% of all chordomas, with most lesions occupying the cranium. Chordomas also can occupy all levels of the spine, demonstrating a broad spectrum of neurologic presentation. Optimal treatment aims for gross total resection with accompanying radiation therapy to prevent recurrence. Their aggressive and infiltrative nature makes clinical management challenging, involving multiple disciplines and close monitoring to ensure optimal outcomes. This comprehensive review aims to cover the genetics, demographics, pathogenesis, neurologic sequelae, radiological considerations, chemotherapeutic management, surgical management, and post-operative considerations of pediatric chordoma patients.

Prognostic nutritional index as a prognostic factor in lung cancer patients receiving chemotherapy: a systematic review and meta-analysis.

Lung cancer is one of the leading causes of morbidity and mortality in the world. In the past decade, numerous studies focus on the prognostic nutritional index (i.e., a measure of serum albumin and lymphocyte in peripheral circulation) as a possible biomarker to predict the survival outcomes in cancer patients undergoing chemotherapy. Prognostic nutritional index can reliably predict the survivability outcomes by effectively quantifying the nutritional and immunological status of cancer patients. To date, only one review has attempted to evaluate the impact of the prognostic nutritional index on the survival outcomes in lung cancer patients with certain limitations. The goal of the present systematic review and meta-analysis is to bridge the gap in the literature and evaluate the capacity of the prognostic nutritional index for predicting the survivability outcomes in lung cancer patients undergoing chemotherapy. The aim of the study is to evaluate the impact of prognostic nutritional index scoring on survival outcomes in lung cancer patients undergoing chemotherapy. A systematic academic literature search was performed based on the PRISMA guidelines across Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE databases. A random-effect meta-analysis was performed to evaluate the impact of prognostic nutritional index scoring (i.e., high/low) on survival outcomes (i.e., progression-free survival, overall survival) in lung cancer patients undergoing chemotherapy. From 963 studies, 16 eligible studies with 4250 lung cancer patients (62.32 ± 5.08 years) undergoing chemotherapy were included. Our meta-analysis revealed worse mortality outcomes in terms of progression-free survival (HR: 1.31) and overall survival (1.21) for the group with a low prognostic nutritional index score as compared to the group with a high prognostic nutritional index score in lung cancer patients undergoing chemotherapy. Subsequent subgroup analyses further demonstrated markedly worse outcomes for progression-free survival (1.32) and overall survival (1.52) in non-small lung cancer patients with lower prognostic nutritional index scores. We provide preliminary evidence suggesting that lower prognostic nutrition index scores are associated with worse survivability outcomes (progression-free survival and overall survival) in lung cancer patients undergoing chemotherapy. We also show that lower prognostic nutrition index scores correlate with even worse survival outcomes in patients with non-small lung cancer histological subtype of lung cancer. These findings should help clinicians to stratify the risks associated with the chemotherapeutic management of lung cancer patients.

Effectiveness of Topical Chemotherapy in Pigmented and Scamous Lesions of the Ocular Surface: Literature Review

The standard of care for the treatment of ocular surface lesions seems to have changed from surgery to topical chemotherapeutic agents as supplements to it or even as sole therapy, despite the scarcity of long-term studies in the published literature. A search in the academic search engines of PubMed, Google academic and Cochrene, of articles published in English language from the years 1997 to 2020 on chemotherapeutic management of ocular surface diseases.

Neoadjuvant and Adjuvant Chemotherapeutic Strategy of Colorectal Mixed Adeno-Neuroendocrine Carcinomas.

Mixed adeno-neuroendocrine carcinomas (MANEC) is a rare pathological diagnosis characterized by the presence of both adeno-carcinomatous and neuroendocrine differentiation with each component comprising 30% of the tumor. This literature review is aimed at the extraction of all existing clinical studies and reviews on colorectal MANEC so as to ensure that a suitable chemotherapeutic regimen is chosen to improve survival outcomes and prognosis of the disease. Parallel search strategies were employed to extract past 10 years articles from PubMed, PubMed Central and Google Scholar databases. A total of 30 records consisting of one clinical trial, five retrospective cohort studies, one case control study, one case series, 16 case reports and six review papers were shortlisted. Chemotherapeutic regimens that were administered as an adjuvant and a neoadjuvant therapy were analyzed with their survival outcomes. The overall survival rate of those administered with neoadjuvant and adjuvant therapy can be as high as 57.4% and 69%, respectively. Multiple chemotherapeutic regimens were employed in colorectal MANEC and superiority of one regimen over the other can’t be established. Any drug or combination of drugs that is responsive against either of the MANEC components is found to be effective against the tumor. However, excellent responsiveness has been found with 5-fluorouracil regimens as a neoadjuvant therapy and platinum-based combinations as an adjuvant therapy. XELOX, streptozocin and S1 regimens also prove to be drugs of choice in aggressive and metastasized disease conditions. Our analysis allows for improved chemotherapeutic management of individuals with colorectal MANEC and establishes an increased potential for use of streptozocin therapy in the clinical setting. However, newer drugs like amrubicin require further research prior to describing its efficacy in colorectal MANEC.

Treatment of Canine Transmissible Venereal Tumour using Different Surgico-chemotherapeutic Protocols

Background: Canine transmissible venereal tumour (CTVT) also known as infectious sarcoma, venereal granuloma, transmissible lymphosarcoma or sticker tumour is usually transmitted through coitus and mainly affects the external genitalia of young sexually matured dogs. Surgery, chemotherapy, radiotherapy and immunotherapy are considered as effective treatment protocols. Therefore, depending upon the availability present study was designed to investigate the efficacy of different surgico-chemotherapeutic protocols for treatment of canine transmissible venereal tumour.Methods: The study was conducted during January 2018 to July 2018 at the Teaching Veterinary Clinical Complex (TVCC) and Department of Veterinary Surgery and Radiology, College of Veterinary Science and A.H., Anjora, Durg (C.G.) on 18 canines of various breed, irrespective of age, sex and divided into three groups consisting 6 animals in each group. Group A was treated with surgical excision of tumour only where as Group B and Group C were treated with surgical excision of tumour followed by administration of Doxorubicin (30mg/m2) BSA and Vincristine sulphate (0.025 mg/kg) intravenously alongwith DNS at 7th and 14th post-operative days respectively. Different physiological and haemato-biochemical parameters (Hb, PCV, TLC, TPC, DLC, serum glucose, TSP, SUN, SC, ALT, AST and ALP) were recorded preoperatively, postoperatively and after chemotherapy at 10th, 30th and 60th days intervals.Result: The present investigation showed transient changes in physiological and haemato-biochemical parameters before, post surgery and post chemotherapeutic management and was within normal range. Histopathological examination revealed confluent sheet of tumour cells arranged in large round oval or polyhedral shaped distributed in tight clusters or cords. Group A showed mild to moderated reoccurrence while Group B showed minimum reoccurrence. Group C showed no reoccurrence. Thus, surgery combined with vincristine therapy is most effective for treating dogs suffering with transmissible venereal tumour.

Ascorbate-induced oxidative stress mediates TRP channel activation and cytotoxicity in human etoposide-sensitive and -resistant retinoblastoma cells

AbstractThere are indications that pharmacological doses of ascorbate (Asc) used as an adjuvant improve the chemotherapeutic management of cancer. This favorable outcome stems from its cytotoxic effects due to prooxidative mechanisms. Since regulation of intracellular Ca2+ levels contributes to the maintenance of cell viability, we hypothesized that one of the effects of Asc includes disrupting regulation of intracellular Ca2+ homeostasis. Accordingly, we determined if Asc induced intracellular Ca2+ influx through activation of pertussis sensitive Gi/o-coupled GPCR which in turn activated transient receptor potential (TRP) channels in both etoposide-resistant and -sensitive retinoblastoma (WERI-Rb1) tumor cells. Ca2+ imaging, whole-cell patch-clamping, and quantitative real-time PCR (qRT-PCR) were performed in parallel with measurements of RB cell survival using Trypan Blue cell dye exclusion. TRPM7 gene expression levels were similar in both cell lines whereas TRPV1, TRPM2, TRPA1, TRPC5, TRPV4, and TRPM8 gene expression levels were downregulated in the etoposide-resistant WERI-Rb1 cells. In the presence of extracellular Ca2+, 1 mM Asc induced larger intracellular Ca2+ transients in the etoposide-resistant WERI-Rb1 than in their etoposide-sensitive counterpart. With either 100 µM CPZ, 500 µM La3+, 10 mM NAC, or 100 µM 2-APB, these Ca2+ transients were markedly diminished. These inhibitors also had corresponding inhibitory effects on Asc-induced rises in whole-cell currents. Pertussis toxin (PTX) preincubation blocked rises in Ca2+ influx. Microscopic analyses showed that after 4 days of exposure to 1 mM Asc cell viability fell by nearly 100% in both RB cell lines. Taken together, one of the effects underlying oxidative mediated Asc-induced WERI-Rb1 cytotoxicity stems from its promotion of Gi/o coupled GPCR mediated increases in intracellular Ca2+ influx through TRP channels. Therefore, designing drugs targeting TRP channel modulation may be a viable approach to increase the efficacy of chemotherapeutic treatment of RB. Furthermore, Asc may be indicated as a possible supportive agent in anti-cancer therapies.Ascorbate can act as an oxidant to induce tumor cell death at a pharmacological dose. Here the authors show that this response is associated with increases in GPCR Gi/o activity. This effect promotes rises in intracellular Ca2+ influx through transient receptor potential channel activity in retinoblastoma cells.

Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome

The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r= 0.726, P < .001) and AJCC 8th edition T-stage (r= 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P= .007). The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

Abstract 15488: Epidemiological Profile of Cardiovascular Risk Factors and Outcomes in Patients With Solid Organ and Haematological Malignancies

Introduction: Chemotherapy remains the cornerstone in the management of solid organ malignancies (SOM) and hematological malignancies (HM). Although life-prolonging, it is not without cost, with heart failure and arrhythmia becoming increasingly recognised complications of treatment. Although there is significant overlap in the chemotherapeutic management of SOM and HM, epidemiological information on the differential prevalence of baseline cardiovascular risk factors and outcomes in these populations is scarce. Hypothesis: A differential cardiovascular risk profile and clinical course will be appreciated in patients with SOM and HM undergoing chemotherapy. Methods: Retrospective observational study design. Patients admitted to our institution undergoing chemotherapy for SOM (2014-2018) or HM (2012-2015) were reviewed. Baseline demographic and clinical data was collated and patients were followed for up to five years following chemotherapy for occurrence of major adverse cardiac events (MACE) defined as the development of new-onset heart failure or arrhythmia. Results: 545 hematology and 435 oncology patients with malignancy were assessed. Compared to those with HM, those treated for SOM had a poorer cardiovascular risk profile (table 1). At mean follow-up period of 22.8±17.8 months, no significant difference in the incidence of the composite endpoint (9.4% vs 9.0%, p=0.45) or its components was observed. Higher rates of anthracycline therapy was observed in patients with HM (100% vs 17%, p &lt; 0.01), however its use did not have a differential effect on MACE (12% vs 9%, p=0.25). Conclusions: Compared to patients treated for HM, patients with SOM had a greater burden of cardiovascular risk factors and lower use of anthracycline chemotherapy. Despite this, MACE occurred at similar rates in both groups. The use of anthracyclines was not associated with the development of MACE, suggesting alternative pathways contributing to its development.