DR. B.R.A. Institute Rotary Cancer Hospital

Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family having tyrosine kinase activity. Dimerization of the receptor results in the autophosphorylation of tyrosine residues within the cytoplasmic domain of the receptors and initiates a variety of signaling pathways leading to cell proliferation and tumorigenesis. Amplification or overexpression of HER2 occurs in approximately 15-30% of breast cancers and 10-30% of gastric/gastroesophageal cancers and serves as a prognostic and predictive biomarker. HER2 overexpression has also been seen in other cancers like ovary, endometrium, bladder, lung, colon, and head and neck. The introduction of HER2 directed therapies has dramatically influenced the outcome of patients with HER2 positive breast and gastric/gastroesophageal cancers; however, the results have been proved disappointing in other HER2 overexpressing cancers. This review discusses the role of HER2 in various cancers and therapeutic modalities available targeting HER2.

Over the past decade, invasive techniques for diagnosing and monitoring cancers are slowly being replaced by non-invasive methods such as liquid biopsy. Liquid biopsies have drastically revolutionized the field of clinical oncology, offering ease in tumor sampling, continuous monitoring by repeated sampling, devising personalized therapeutic regimens, and screening for therapeutic resistance. Liquid biopsies consist of isolating tumor-derived entities like circulating tumor cells, circulating tumor DNA, tumor extracellular vesicles, etc., present in the body fluids of patients with cancer, followed by an analysis of genomic and proteomic data contained within them. Methods for isolation and analysis of liquid biopsies have rapidly evolved over the past few years as described in the review, thus providing greater details about tumor characteristics such as tumor progression, tumor staging, heterogeneity, gene mutations, and clonal evolution, etc. Liquid biopsies from cancer patients have opened up newer avenues in detection and continuous monitoring, treatment based on precision medicine, and screening of markers for therapeutic resistance. Though the technology of liquid biopsies is still evolving, its non-invasive nature promises to open new eras in clinical oncology. The purpose of this review is to provide an overview of the current methodologies involved in liquid biopsies and their application in isolating tumor markers for detection, prognosis, and monitoring cancer treatment outcomes.

Deregulated protein tyrosine kinase activity is central to the pathogenesis of human cancers. Targeted therapy in the form of selective tyrosine kinase inhibitors (TKIs) has transformed the approach to management of various cancers and represents a therapeutic breakthrough. Imatinib was one of the first cancer therapies to show the potential for such targeted action. Imatinib, an oral targeted therapy, inhibits tyrosine kinases specifically BCR-ABL, c-KIT, and PDGFRA. Apart from its remarkable success in CML and GIST, Imatinib benefits various other tumors caused by Imatinib-specific abnormalities of PDGFR and c-KIT. Imatinib has also been proven to be effective in steroid-refractory chronic graft-versus-host disease because of its anti-PDGFR action. This paper is a comprehensive review of the role of Imatinib in oncology.

Cancer is one of the leading causes of death and significantly burdens the healthcare system. Due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. The use of natural products as anticancer agents is an acceptable therapeutic approach due to accessibility, applicability, and reduced cytotoxicity. Natural products have been an incomparable source of anticancer drugs in the modern era of drug discovery. Along with their derivatives and analogs, natural products play a major role in cancer treatment by modulating the cancer microenvironment and different signaling pathways. These compounds are effective against several signaling pathways, mainly cell death pathways (apoptosis and autophagy) and embryonic developmental pathways (Notch pathway, Wnt pathway, and Hedgehog pathway). The historical record of natural products is strong, but there is a need to investigate the current role of natural products in the discovery and development of cancer drugs and determine the possibility of natural products being an important source of future therapeutic agents. Many target-specific anticancer drugs failed to provide successful results, which accounts for a need to investigate natural products with multi-target characteristics to achieve better outcomes. The potential of natural products to be promising novel compounds for cancer treatment makes them an important area of research. This review explores the significance of natural products in inhibiting the various signaling pathways that serve as drivers of carcinogenesis and thus pave the way for developing and discovering anticancer drugs.

IMPORTANCE: Efficacious ERBB2 (formerly HER2 or HER2/neu)-directed treatments, in addition to trastuzumab and lapatinib, are needed. OBJECTIVE: To determine whether neratinib, an irreversible pan-ERBB tyrosine kinase inhibitor, plus paclitaxel improves progression-free survival compared with trastuzumab plus paclitaxel in the first-line treatment of recurrent and/or metastatic ERBB2-positive breast cancer. DESIGN, SETTING, AND PARTICIPANTS: In the randomized, controlled, open-label NEfERT-T trial conducted from August 2009 to December 2014 at 188 centers in 34 countries in Europe, Asia, Africa, and North America, 479 women with previously untreated recurrent and/or metastatic ERBB2-positive breast cancer were randomized to 1 of 2 treatment arms (neratinib-paclitaxel [n = 242] or trastuzumab-paclitaxel [n = 237]). Women with asymptomatic central nervous system metastases were eligible, and randomization was stratified by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. INTERVENTIONS: Women received neratinib (240 mg/d orally) or trastuzumab (4 mg/kg then 2 mg/kg weekly), each combined with paclitaxel (80 mg/m2 on days 1, 8, and 15 every 28 days). Primary prophylaxis for diarrhea was not mandatory. MAIN OUTCOME AND MEASURES: The primary outcome was progression-free survival. Secondary end points were response rate, clinical benefit rate, duration of response, frequency, and time to symptomatic and/or progressive central nervous system lesions, and safety. RESULTS: The intent-to-treat population comprised 479 women 18 years or older (neratinib-paclitaxel, n = 242; trastuzumab-paclitaxel, n = 237) randomized and stratified in their respective treatment arms by prior trastuzumab and lapatinib exposure, hormone-receptor status, and region. Median progression-free survival was 12.9 months (95% CI, 11.1-14.9) with neratinib-paclitaxel and 12.9 months (95% CI, 11.1-14.8) with trastuzumab-paclitaxel (hazard ratio [HR], 1.02; 95% CI, 0.81-1.27; P =.89). With neratinib-paclitaxel, the incidence of central nervous system recurrences was lower (relative risk, 0.48; 95% CI, 0.29-0.79; P = .002) and time to central nervous system metastases delayed (HR, 0.45; 95% CI, 0.26-0.78; P = .004). Common grade 3 to 4 adverse events were diarrhea (73 of 240 patients [30.4%] with neratinib-paclitaxel and 9 of 234 patients [3.8%] with trastuzumab-paclitaxel), neutropenia (31 patients [12.9%] vs 34 patients [14.5%]) and leukopenia (19 patients [7.9%] vs 25 patients [10.7%]); no grade 4 diarrhea was observed. CONCLUSIONS AND RELEVANCE: In first-line ERBB2-positive metastatic breast cancer, neratinib-paclitaxel was not superior to trastuzumab-paclitaxel in terms of progression-free survival. In spite of similar overall efficacy, neratinib-paclitaxel may delay the onset and reduce the frequency of central nervous system progression, a finding that requires a larger study to confirm. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00915018.

PURPOSE: We designed this study to evaluate efficacy of modified gemcitabine and oxaliplatin (mGEMOX) over best supportive care (BSC) or fluorouracil (FU) and folinic acid (FA) in unresectable gall bladder cancer (GBC). PATIENTS AND METHODS: Patients with unresectable GBC were enrolled for single center randomized study. Arm A, BSC; arm B, FU 425 mg/m(2) and FA 20 mg/m(2) intravenous (IV) bolus weekly for 30 weeks (FUFA); arm C, gemcitabine 900 mg/m(2) and oxaliplatin 80 mg/m(2) IV infusion on days 1 and 8 every 3 weeks for maximum of six cycles. Eighty-one patients were randomly assigned, arms A (n = 27), B (n = 28), and C (n = 26). RESULTS: Complete response plus partial response in the three groups was 0 (0%), four (14.3%), and eight (30.8%) respectively (P < .001). Two patients in the mGEMOX arm and one patient in the FUFA arm underwent curative resection after chemotherapy. One patient in the mGEMOX arm had complete pathologic response. Median overall survival (OS) was 4.5, 4.6, and 9.5 months for the BSC, FUFA, and mGEMOX arms (P = .039), respectively. Progression-free survival (PFS) was 2.8, 3.5, and 8.5 months for the three groups (P < .001). There was no difference in grade 3/4 toxicities in the chemotherapy arms except transaminitis, which was more prevalent in mGEMOX arm (P = .04). Two patients in the FUFA arm and 10 patients in the mGEMOX arm had grade 3 or 4 myelosuppression. Two patients in the mGEMOX group had neutropenic fever that resolved with antibiotics. CONCLUSION: This randomized controlled trial confirmed the efficacy of chemotherapy (mGEMOX) compared with BSC and FUFA in improving OS and PFS in unresectable GBC.

CONTEXT: Few efforts have attempted to quantify how well countries deliver end-of-life (EOL) care. OBJECTIVES: To score, grade, and rank countries (and Hong Kong and Taiwan) on the quality of EOL care based on assessments from country experts using a novel preference-based scoring algorithm. METHODS: We fielded a survey to country experts around the world, asking them to assess the performance of their country on 13 key indicators of EOL care. Results were combined with preference weights from caregiver-proxies of recently deceased patients to generate a preference-weighted summary score. The scores were then converted to grades (from A-F) and a ranking was created for all included countries. RESULTS: The final sample included responses from 181 experts representing 81 countries with 2 or more experts reporting. The 6 countries who received the highest assessment scores and a grade of A were United Kingdom, Ireland, Taiwan, Australia, Republic of Korea, and Costa Rica. Only Costa Rica (upper middle) is not a high income country. Not until Uganda (ranked 31st) does a low-income country appear on the ranking. Based on the assessment scores, twenty-one countries received a failing grade, with only two - Czech Republic (66th), and Portugal (75th) - being high income countries. CONCLUSION: This study provides an example of how a preference-based scoring algorithm and input from key stakeholders can be used to assess EOL health system performance. Results highlight the large disparities in assessments of the quality of EOL care across countries, and especially between the highest income countries and others.

BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is biologically an aggressive tumor for which the treatment of choice is the surgery. We reviewed the clinical profile, diagnostic methods, treatment patterns, and outcome of twenty-four MPNST patients in this study. PATIENTS AND METHODS: A retrospective analysis of 24 MPNST patients, treated from 1994 to 2002, in the department of Surgical Oncology at All India Institute of Medical Sciences, New Delhi, was done. A combination of gross, histopathological and immunohistochemical findings, and proliferation markers (MIB1) were considered for diagnosis and grade of the MPNST. Survival analysis was done by the Kaplan-Meier method and differences were evaluated with the log-rank test. Multivariate analysis was carried out by using Cox's proportional hazards model by using SPSS (Version 9, Chicago, Illinois) software. RESULTS: MPNST constituted 12% of all soft tissue sarcomas, where 21% (5/24) of patients had associated Von Recklinghausen's disease (VRHD). A higher incidence of male preponderance and multifocal MPNST were noted in the present series. At a mean follow-up of 38 months, 13 (54 %) patients had relapse of disease and 5-year over all and disease free survival were 58% and 35% respectively. In univariate analysis, sex (p = 0.05), tumor depth (p < 0.03), and cellular differentiation (p < 0.002) were shown to be adverse prognostic factors for disease free survival and sex (p = 0.04), cellular differentiation (p < 0.0004), and tumor grade (p = 0.05) for overall survival. However, in multivariate analysis, cellular differentiation (p < 0.005) and tumor grade (p < 0.01) emerged as independent prognostic factors for both disease free and overall survival, respectively. Postoperative radiotherapy (RT) has shown a definite role in both disease free and overall survival in this study. CONCLUSION: MPNSTs constituted a significant proportion (12%) of soft tissue sarcoma in our medical center. Heterogeneous differentiation and multifocality of the tumor were few distinct features of MPNST. Sex and cellular differentiation were noticed as the new adverse prognostic factors and adjuvant radiotherapy has been proved to be a significant treatment tool in the current series.

Colorectal cancer (CRC) is a predominant life-threatening cancer, with liver and peritoneal metastases as the primary causes of death. Intestinal inflammation, a known CRC risk factor, nurtures a local inflammatory environment enriched with tumor cells, endothelial cells, immune cells, cancer-associated fibroblasts, immunosuppressive cells, and secretory growth factors. The complex interactions of aberrantly expressed cytokines, chemokines, growth factors, and matrix-remodeling enzymes promote CRC pathogenesis and evoke systemic responses that affect disease outcomes. Mounting evidence suggests that these cytokines and chemokines play a role in the progression of CRC through immunosuppression and modulation of the tumor microenvironment, which is partly achieved by the recruitment of immunosuppressive cells. These cells impart features such as cancer stem cell-like properties, drug resistance, invasion, and formation of the premetastatic niche in distant organs, promoting metastasis and aggressive CRC growth. A deeper understanding of the cytokine- and chemokine-mediated signaling networks that link tumor progression and metastasis will provide insights into the mechanistic details of disease aggressiveness and facilitate the development of novel therapeutics for CRC. Here, we summarized the current knowledge of cytokine- and chemokine-mediated crosstalk in the inflammatory tumor microenvironment, which drives immunosuppression, resistance to therapeutics, and metastasis during CRC progression. We also outlined the potential of this crosstalk as a novel therapeutic target for CRC. The major cytokine/chemokine pathways involved in cancer immunotherapy are also discussed in this review.

Neuropathic pain is difficult to diagnose and difficult to treat with certainty. So the aim of the study was to evaluate comparative clinical efficacy of pregabaline with amitriptyline and gabapentin in neuropathic cancer pain. A total of 120 patients with cancer having severe neuropathic cancer pain were enrolled in the study after taking approval from Institutional Ethics Committee and divided in to 4 groups: group AT-amitriptyline, group GB-gabapentin, group PG-pregabalin, and group PL-placebo. Oral morphine was used for rescue analgesic for continued pain. Pain score (Visual Analogue scale) and secondary outcome measures such as intensity of lancinating, dysesthesia, and burning on numerical rating scale, Global satisfaction score (GSS), Eastern Co-operative Oncology Group scoring (ECOG), and adverse effects were assessed. At the end of study there was significant decrease in pain score in group PG as compared to the other groups; group AT (P = .003), group GB (P = .042), and group PL (P = .024). Percentage of patients with lancinating pain and dysesthesia were significantly less in group PG as compared to groups GB and PL. All the patients in group PL needed rescue morphine. After 4 visits, maximum improvement in ECOG scoring and GSS scoring was observed in group PG patients. Our results suggested that all antineuropathic drugs are effective in relieving cancer-related neuropathic pain. There was statistically and clinically significant morphine sparing effect of pregabaline in relieving neuropathic cancer pain and neuropathic symptoms as compared to other antineuropathic drugs.

Early-stage detection of leukemia is a critical determinant for successful treatment of the disease and can increase the survival rate of leukemia patients. The factors limiting the current screening approaches to leukemia include low sensitivity and specificity, high costs, and a low participation rate. An approach based on novel and innovative biomarkers with high accuracy from peripheral blood offers a comfortable and appealing alternative to patients, potentially leading to a higher participation rate.Recently, non-coding RNAs due to their involvement in vital oncogenic processes such as differentiation, proliferation, migration, angiogenesis and apoptosis have attracted much attention as potential diagnostic and prognostic biomarkers in leukemia. Emerging lines of evidence have shown that the mutational spectrum and dysregulated expression of non-coding RNA genes are closely associated with the development and progression of various cancers, including leukemia. In this review, we highlight the expression and functional roles of different types of non-coding RNAs in leukemia and discuss their potential clinical applications as diagnostic or prognostic biomarkers and therapeutic targets.

Lung cancer has become a global problem, from a rare disease to an emerging public health issue. The current data of GLOBOCAN 2018, indicates that this disease has recorded highest mortality among all types of cancer. The etiological factors of lung cancer have become more multiplex because of increasing industrialization and environmental pollution around the world, especially in India. There is a rise in incidence of lung cancer among non-smokers and this can be attributed to environmental and occupational exposure to various kinds of hazardous substances. Target mutations are high in Lung cancer among non-smokers when compared to smokers. Some developed countries have guidelines and policies for prevention and control of risk factors focusing on these issues. Intervention aiming for primary prevention can be an important and cost-effective tool in developing countries to deal with increasing incidence of lung cancer. There is a need to define high risk group among non-smokers after taking into account environmental and occupational determinants as important risk factors. Research on etiology of lung cancer and prevention provides evidence to work on global incidence and prevalence of lung cancer, and for designing cost effective lung cancer prevention strategies. Research in the area of lung cancer prevention should be considered to recognize the areas where action is required to prevent environment and occupation related lung cancer. The government and occupational health and safety organizations have taken many steps in the last few years that can help to protect workers from these exposures. But the dangers are still there, so there is a need to do more to limit these exposures around workplace. This whole situation guides us to advocate population-based intervention along with policy implementation.

Abstract Purpose Chemotherapy‐induced nausea and vomiting (CINV) are major adverse effects of chemotherapy. Ginger has been used in postoperative and pregnancy‐induced nausea and vomiting. Data on its utility in reducing CINV in children and young adults are lacking. Patients and Methods Sixty chemotherapy cycles of cisplatin/doxorubicin in bone sarcoma patients were randomized to ginger root powder capsules or placebo capsules as an additional antiemetic to ondensetron and dexamethasone in a double‐blind design. Acute CINV was defined as nausea and vomiting occurring within 24 hr of start of chemotherapy (days 1–4) and delayed CINV as that occurring after 24 hr of completion of chemotherapy (days 5–10). CINV was evaluated as per Edmonton's Symptom Assessment Scale and National Cancer Institute criteria respectively. Results Acute moderate to severe nausea was observed in 28/30 (93.3%) cycles in control group as compared to 15/27 (55.6%) cycles in experimental group ( P = 0.003). Acute moderate to severe vomiting was significantly more in the control group compared to the experimental group [23/30 (76.7%) vs. 9/27 (33.33%) respectively ( P = 0.002)]. Delayed moderate to severe nausea was observed in 22/30 (73.3%) cycles in the control group as compared to 7/27 (25.9%) in the experimental group ( P &lt; 0.001). Delayed moderate to severe vomiting was significantly more in the control group compared to the experimental group [14/30 (46.67%) vs. 4/27 (14.81%) ( P = 0.022)]. Conclusion Ginger root powder was effective in reducing severity of acute and delayed CINV as additional therapy to ondensetron and dexamethasone in patients receiving high emetogenic chemotherapy (ClinicalTrials.gov identifier: NCT00940368). Pediatr Blood Cancer 2011;56:234–238. © 2010 Wiley‐Liss, Inc.

Coronavirus outbreak has affected thousands of people in at least 186 countries which has affected the cancer care delivery system apart from affecting the overall health system. Cancer patients are more susceptible to coronavirus infection than individuals without cancer as they are in an immunosuppressive state because of the malignancy and anticancer treatment. Oncologists should be more attentive to detect coronavirus infection early, as any type of advanced cancer is at much higher risk for unfavorable outcomes. Oncology communities must ensure that cancer patients should spend more time at home and less time out in the community. Oncologists and other health care professionals involved in cancer care have a critical opportunity to communicate to their patients to pass on right information regarding practice modifications in view of COVID-19 outbreaks. Countries must isolate, test, treat and trace to control the coronavirus pandemic. There is a paucity of information on novel coronavirus infection and its impact on cancer patients and cancer care providers. To date, there is no scientific guideline regarding management of cancer patients in a background of coronavirus outbreak.<br />.

BACKGROUND: MicroRNAs are a class of small non-coding RNAs that regulate mRNA expression at the post - transcriptional level and thereby many fundamental biological processes. A number of methods, such as multiplex polymerase chain reaction, microarrays have been developed for profiling levels of known miRNAs. These methods lack the ability to identify novel miRNAs and accurately determine expression at a range of concentrations. Deep or massively parallel sequencing methods are providing suitable platforms for genome wide transcriptome analysis and have the ability to identify novel transcripts. RESULTS: The results of analysis of small RNA sequences obtained by Solexa technology of normal peripheral blood mononuclear cells, tumor cell lines K562 and HL60 are presented. In general K562 cells displayed overall low level of miRNA population and also low levels of DICER. Some of the highly expressed miRNAs in the leukocytes include several members of the let-7 family, miR-21, 103, 185, 191 and 320a. Comparison of the miRNA profiles of normal versus K562 or HL60 cells revealed a specific set of differentially expressed molecules. Correlation of the miRNA with that of mRNA expression profiles, obtained by microarray, revealed a set of target genes showing inverse correlation with miRNA levels. Relative expression levels of individual miRNAs belonging to a cluster were found to be highly variable. Our computational pipeline also predicted a number of novel miRNAs. Some of the predictions were validated by Real-time RT-PCR and or RNase protection assay. Organization of some of the novel miRNAs in human genome suggests that these may also be part of existing clusters or form new clusters. CONCLUSIONS: We conclude that about 904 miRNAs are expressed in human leukocytes. Out of these 370 are novel miRNAs. We have identified miRNAs that are differentially regulated in normal PBMC with respect to cancer cells, K562 and HL60. Our results suggest that post - transcriptional processes may play a significant role in regulating levels of miRNAs in tumor cells. The study also provides a customized automated computation pipeline for miRNA profiling and identification of novel miRNAs; even those that are missed out by other existing pipelines. The Computational Pipeline is available at the website: http://mirna.jnu.ac.in/deep_sequencing/deep_sequencing.html.

BACKGROUND: Data on the clinical profile of early breast cancer (EBC) from India is scant. Due to differences in genetics, environment, lifestyle, socio-demographic structure and ethnicity, the presentation and behavior of breast cancer in India may be different. AIMS: To analyze the clinical presentation and outcome of EBC patients. SETTINGS AND DESIGN: A single center retrospective study. MATERIALS AND METHODS: Data from 487 EBC patients registered and treated at our institute from 1993 through 1999 were analyzed. Cox's multivariate regression test was used to determine prognostic factors for overall and disease-free survival (OS & DFS). RESULTS: The median age was 47 years and 49.7% patients were pre-menopausal. Ninety-six per cent patients presented with a lump. Stages I, IIa, and IIb comprised 7.8%, 38.8%, and 47.6% respectively. Only 11.3% patients opted for breast-conserving surgery (BCS) while the remaining 88.7% underwent modified radical mastectomy (MRM). Adjuvant chemotherapy was administered to 275 (56.5%), and radiotherapy to 146 (29.9%). Estrogen receptor status was known in 173, of whom 93 (53.7%) were positive. Most patients were prescribed Tamoxifen for 5 years. At a median follow-up of 48 months, 126 (25.9%) patients had relapsed (systemic 107, loco-regional 19) and 94 (19.3%) had died. Five-year DFS and OS were 73% and 78%, respectively. On multivariate analysis, four positive nodes adversely influenced survival (P< 0.01). CONCLUSIONS: The median age at presentation was 47 years, significantly lower than most Western figures. The majority (86.4%) had a lump size > two cm. BCS was done in only 11% and the rest underwent MRM. Nodal involvement was the significant prognostic factor.

Ac-PSMA-617 TAT showed promising disease control rate, even when all other therapeutic options were exhausted, with low treatment-related toxicities.

OBJECTIVE: To study the clinical presentation and survival among Indian children with retinoblastoma (RB) and to determine factors predictive of poor outcome. METHODS: A retrospective review of children newly diagnosed with RB at a tertiary referral centre was undertaken. Demographic and clinical characteristics and treatment outcomes were studied. RESULTS: A total of 600 patients (unilateral 67.6%, bilateral 32.4%) was studied. 61% was boys. The median age at presentation was 29 months (18 months vs 36 months in bilateral and unilateral cases, respectively, p<0.001). leukocoria was most common (83%), followed by proptosis (17%). Tumours were intraocular in 72.3% and extraocular in 27.7% cases. In the intraocular group, 78% were advanced Group D or E disease. Metastasis to the central nervous system was noted in 15.7% of extraocular cases. A statistically significant difference was seen between intraocular and extraocular groups in the median age (24 months vs 37.5 months, p<0.001) and median lag period (2.5 months vs 7 months, p<0.001). The Kaplan-Meier survival probability was 83%, 73% and 65% at 1 year, 2 years and 5 years, respectively. On univariate analysis, age >2 years (p=0.002), lag period >6 months (p=0.004) and extraocular stage (p<0.001) were associated with poor outcome. On multivariate analysis, extraocular invasion was predictive of low survival (HR 5.04, p<0.001). CONCLUSIONS: Delayed presentation is a matter of concern. Improving awareness about the early signs and creating facilities for diagnosing and treating RB at the primary and secondary levels of healthcare are required to reduce mortality and morbidity, and lead to improved outcomes that are comparable with the developed nations.

Esophageal cancer (EC) is a disease often marked by aggressive growth and poor prognosis. Lack of targeted therapies, resistance to chemoradiation therapy, and distant metastases among patients with advanced disease account for the high mortality rate. The tumor microenvironment (TME) contains several cell types, including fibroblasts, immune cells, adipocytes, stromal proteins, and growth factors, which play a significant role in supporting the growth and aggressive behavior of cancer cells. The complex and dynamic interactions of the secreted cytokines, chemokines, growth factors, and their receptors mediate chronic inflammation and immunosuppressive TME favoring tumor progression, metastasis, and decreased response to therapy. The molecular changes in the TME are used as biological markers for diagnosis, prognosis, and response to treatment in patients. This review highlighted the novel insights into the understanding and functional impact of deregulated cytokines and chemokines in imparting aggressive EC, stressing the nature and therapeutic consequences of the cytokine-chemokine network. We also discuss cytokine-chemokine oncogenic potential by contributing to the Epithelial-Mesenchymal Transition (EMT), angiogenesis, immunosuppression, metastatic niche, and therapeutic resistance development. In addition, it discusses the wide range of changes and intracellular signaling pathways that occur in the TME. Overall, this is a relatively unexplored field that could provide crucial insights into tumor immunology and encourage the effective application of modulatory cytokine-chemokine therapy to EC.

INTRODUCTION: Avoidable blindness is a significant public health problem in India. Nationally representative RAAB surveys (Rapid Assessment of Avoidable Blindness) are being conducted periodically in the country to know the current status of blindness in the country. The current study describes the findings from the RAAB survey conducted during 2015-19 in India. METHODOLOGY: A cross-sectional, population-based survey was conducted across the entire country among persons aged 50 years and above using RAAB version 6 methodology. Presenting and pinhole visual acuity was recorded followed by lens examination using a torchlight. In order to estimate the prevalence of blindness and visual impairment in overall population in India, district weights were assigned to each of the 31 surveyed districts and the prevalence was standardized using the RAAB software. RESULTS: The overall weighted, age-gender standardized, prevalence of blindness (presenting visual acuity <3/60 in better eye) in population aged ≥50 years was 1.99% (95% CI 1.94%, 2.13%) and of visual impairment (VI) (presenting visual acuity <6/12 in better eye) was 26.68% (95% CI 26.57-27.17%). On multivariate analysis, adjusted odds ratio showed that blindness was associated with age ≥ 80 years (OR = 20.3, 95% CI: 15.6-26.4) and being illiterate (OR = 5.6, 95% CI: 3.6-8.9). Blindness was not found to be significantly associated with either gender or locality. CONCLUSION: The results of the survey demonstrate that currently more than one fourth of persons aged 50 years and above are visually impaired (PVA<6/12 in better eye) in India. The prevalence of blindness among them is 1.99%, and older age and illiteracy are significantly associated with blindness. Major causes of blindness included cataract (66.2%), corneal opacity (CO) (8.2%), cataract surgical complications (7.2%), posterior segment disorders (5.9%) and glaucoma (5.5%). The proportion of blindness and visual impairment that is due to avoidable causes include 92.9% and 97.4% respectively.