MK591 (Quiflapon), a 5-lipoxygenase inhibitor, kills pancreatic cancer cells via downregulation of protein kinase C-epsilon.

Introduction: Pancreatic tumors and cell lines derived from them exhibit elevated expression of 5-lipoxygenase (5-Lox), whereas non-tumor glands or normal cells do not exhibit this overexpression. Arachidonic acid stimulates pancreatic cancer cell growth via metabolic conversion through the 5-Lox pathway, and inhibition of 5-Lox activity decreases the viability of pancreatic cancer cells. However, the downstream signaling mechanisms through which 5-Lox exerts its effects on the survival of pancreatic cancer cells remain to be elucidated. Methods: The effects of 5-Lox inhibition on cell proliferation, apoptosis, and invasive potential were investigated in pancreatic cancer cells. The protein expression was analyzed by Western blot. Apoptosis was analyzed by Annexin-V binding assay and by detecting the degradation of chromatin-DNA to nucleosomal fragments. The protein kinase C-epsilon (PKCε) activity was measured by an immunoprecipitation-kinase assay. The in vivo effects of MK591 were evaluated in pancreatic tumor xenograft model. Results: MK591, a specific inhibitor of 5-Lox activity, killed pancreatic cancer cells via induction of apoptosis, involving externalization of phosphatidylserine, cleavage of PARP (poly-ADP ribose polymerase) and degradation of chromatin DNA to nucleosomes. MK591 effectively blocked in vitro invasion and soft-agar colony formation by pancreatic cancer cells and decreased pancreatic tumor growth in nude mice xenografts. Furthermore, inhibition of 5-Lox downregulated K-Ras and inhibited phosphorylation of c-Raf and ERKs. Interestingly, 5-Lox inhibition induced apoptosis in pancreatic cancer cells without the inhibition of Akt but the protein level of PKCε was dramatically downregulated. Furthermore, inhibition of 5-Lox decreased the phosphorylation of Stat3 at Serine-727. Pre-treatment of pancreatic cancer cells with peptide activators of PKCε prevented apoptosis induced by 5-Lox inhibition, suggesting that the mechanism by which 5-Lox inhibition causes cell death in pancreatic cancer involves downregulation of PKCε. The combination of low doses of MK591 and gemcitabine synergistically reduced the oncogenic phenotype and killed pancreatic cancer cells by inducing apoptosis. Discussion: These findings indicate that inhibition of 5-Lox interrupts an Akt-independent, PKCε-dependent survival mechanism in pancreatic cancer cells and suggest that metabolism of arachidonic acid through the 5-Lox pathway plays an integral part in the survival of pancreatic cancer cells via signaling through PKCε, an oncogenic, pro-survival serine/threonine kinase.

Long-Term Follow-Up of Phase I Trial of Oncolytic Adenovirus-Mediated Cytotoxic and Interleukin-12 Gene Therapy for Treatment of Metastatic Pancreatic Cancer.

The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.

Laparoscopic Correction of Isthmocele and Cesarean Scar Endometriosis: A Report of a Successful Pregnancy and Treatment of Subfertility.

We present a case of subfertility due to isthmocele and cesarean scar endometriosis with a successful pregnancy following laparoscopic repair. This case report is of a 35-year-old female (para 1, living 1) who presented to the gynecological outpatient department with complaints of lower abdominal pain, irregular vaginal bleeding for three months, and subfertility. She was suspected to have isthmocele and endometriosis at the site of the cesarean scar with seroma formation. She underwent a hysteroscopy and laparoscopic excision of the cyst at the site of the cesarean scar with the repair of the cesarean scar defect. Diagnosis of scar endometriosis was confirmed on histopathology. She successfully became pregnant after one year and had a full-term pregnancy and delivered via cesarean section. Cesarean scar defect, also known as isthmocele, emerges as a notable complication following cesarean delivery, often linked with secondary infertility. Other associated complications of scar defect are prolonged menstrual bleeding, dysmenorrhea, dyspareunia, and chronic pelvic pain. The laparoscopic reparation of the uterine scar defect proves to be a successful approach in addressing secondary infertility and subfertility issues. Individuals with a prior cesarean section history, expressing concerns about secondary infertility and distressing complaints, require a thorough examination of the uterine scar before embarking on future pregnancy plans. Scar endometriosis is an uncommon medical condition and can worsen patient symptoms and lead to further complications. Diagnosis is often established following the excision of the lesion and subsequent histopathological examination. Prompt management can relieve patient symptoms and prevent further complications.

Characterization of Pre-Breeding Wheat (Triticum aestivum L.) Germplasm for Stripe Rust Resistance Using Field Phenotyping and Genotyping.

Wheat is highly affected by stripe rust disease, particularly under cooler environments, and the losses can reach up to 100 percent depending on the intensity of infection and the susceptibility of the genotype. The most effective method to manage this disease is the use of resistant varieties. In the present study, 192 wheat genotypes were evaluated for stripe rust resistance under field conditions and also in a laboratory using molecular markers. These lines included pre-breeding germplasm developed for rust resistance and some high-yielding commercially grown wheat varieties. Out of 192 genotypes, 53 were found to be resistant, and 29 showed moderate resistance reaction under field conditions, whereas the remaining genotypes were all either moderately susceptible or susceptible. Under controlled conditions, out of 109 genotypes, only 12 were found to be resistant to all the six virulent/pathogenic pathotypes. Additionally, a selection of 97 genotypes were found resistant in field screening and were subjected to molecular validation using the markers linked to major R-genes, viz., Yr5, Yr10, Yr15 and Yr17. Nine genotypes possessed the Yr5 gene, twelve had the Yr10 gene, fourteen had the Yr15 gene and thirty-two had the Yr17 gene. The resistance genes studied in the current study are effective in conferring resistance against stripe rust disease. The genotypes identified as resistant under both field and controlled conditions can be used as sources in stripe rust resistance breeding programs.

Acute Disseminated Encephalomyelitis in a Six-Year-Old Child: A Case Report.

Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune demyelinating disorder that primarily affects the central nervous system (CNS). It is characterized by an acute inflammatory response targeting the myelin sheath surrounding nerve fibers in the brain and spinal cord. The exact mechanism of ADEM is not fully understood, but it is believed to involve an abnormal immune response that leads to the activation of immune cells and subsequent inflammation within the CNS. This immune-mediated attack results in the destruction of myelin, impairing the transmission of nerve signals and causing a wide range of neurological symptoms. This is a case of a six-year-old girl with no notable medical history presented with complaints of a fever and headache for the last month, in addition to difficulty walking for 20 days and speaking for 14 days. On CNS examination, the right upper and lower limbs' power was reduced, and the Babinski sign was seen in both lower limbs. Both sides of the triceps and knee showed increased reflexes, whereas both sides of the ankle showed decreased reflexes. Magnetic resonance imaging (MRI) showed multiple T1 hypointensities and T2-weighted fluid-attenuated inversion recovery (T2-FLAIR) hyperintensities in the subcortical white matter of the bilateral frontal and parietal lobes, bilateral cerebellar peduncles, corpus callosum, pons, and midbrain. Our case report aims to raise awareness and aid in the early recognition of ADEM because prompt recognition, accurate diagnosis, and appropriate management are essential to minimizing neurological damage and promoting favorable outcomes in affected individuals.

Gene expression of near-isogenic lines (NILs) carrying blast resistance genes Pi9 and Pi54 in the background of rice cultivar Mushk Budji.

BACKGROUND: Kashmir valley, India is a homeland to rice landraces like Zag, Nunbeoul, Qadirbeigh, Kawkadur, Kamad, Mushk Budji, etc., generally characterized by short grains, aroma, earliness and cold tolerance. Mushk Budji is a commercially important speciality rice known for its taste and aroma, nonetheless, is extremely vulnerable to blast disease. Through the use of the marker-assisted backcrossing (MABC) approach, a set of 24 Near-isogenic lines (NILs) was created, and the lines with the highest background genome recovery were chosen. The expression analysis was carried out for the component genes and other eight pathway genes related to blast resistance. RESULTS: The major blast resistance genes Pi9 (from IRBL-9W) and Pi54 (from DHMAS 70Q 164-1b) were incorporated following simultaneous-but-step-wise MABC. The NILs harbouring genes Pi9 + Pi54, Pi9 and Pi54 expressed resistance to isolate (Mo-nwi-kash-32) under controlled and natural field conditions. The loci controlling ETI (effector triggered immunity) included the gene Pi9 and showed 61.18 and 60.27 fold change in relative gene expression in Pi54 + Pi9 and Pi9 carrying NILs against RP Mushk Budji. Pi54 was up regulated and showed 41 and 21 fold change in relative gene expression for NIL-Pi54 + Pi9 and NIL-Pi54, respectively. Among the pathway genes, LOC_Os01g60600 (WRKY 108) recorded 8 and 7.5 fold up regulation in Pi9 and Pi54 NILs. CONCLUSION: The NILs showed recurrent parent genome recovery (RPG) per cent of 81.67 to 92.54 and were on par in performance to recurrent parent Mushk Budji. The lines were utilized to study the expression of the loci controlling WRKYs, peroxidases and chitinases that confer overall ETI response.

Development of Clindamycin Loaded Oral Microsponges (Clindasponges) for Antimicrobial Enhancement: In Vitro Characterization and Simulated in Vivo Studies.

Clindamycin phosphate (CLP) is a broad-spectrum antibiotic that is used widely for different types of infections. It has a short half-life and hence it should be taken every six hours to ensure adequate antibiotic blood concentration. On the other hand, microsponges are extremely porous polymeric microspheres, offering the prolonged controlled release of the drug. The present study aims to develop and evaluate innovative CLP-loaded microsponges (named Clindasponges) to prolong and control the drug release and enhance its antimicrobial activity, consequently improving patient compliance. The clindasponges were fabricated successfully by quasi-emulsion solvent diffusion technique using Eudragit S100 (ES100) and ethyl cellulose (EC) as carriers at various drug-polymer ratios. Several variables were optimized for the preparation technique including the type of solvent, stirring time, and stirring speed. The clindasponges were then characterized in terms of particle size, production yield, encapsulation efficiency, scanning electron microscopy, Fourier Transform Infrared Spectroscopy analysis, in vitro drug release with kinetic modeling, and antimicrobial activity study. Moreover, in vivo, pharmacokinetics parameters of CLP from the candidate formula were simulated based on the convolution method and in vitro-in vivo correlation (IVIVC-Level A) was built up successfully. Uniform spherical microsponges with 82.3 µm mean particle size with a porous spongy structure were evident. ES2 batch exhibited the highest production yield and encapsulation efficiency (53.75 and 74.57%, respectively) and it was able to exhaust 94% of the drug at the end of 8 h of the dissolution test. The release profile data of ES2 was best fitted to Hopfenberg kinetic model. ES2 was significantly (p < 0.05) effective against Staphylococcus aureus and Escherichia coli compared to the control. Also, ES2 displayed a twofold increase in the simulated area under the curve (AUC) compared to the reference marketed product.

Potential Phytochemicals for Prevention of Familial Breast Cancer with BRCA Mutations.

Breast cancer has remained a global challenge and the second leading cause of cancer mortality in women and family history. Hereditary factors are some of the major risk factors associated with breast cancer. Out of total breast cancer cases, 5-10% account only for familial breast cancer, and nearly 50% of all hereditary breast cancer are due to BRCA1/BRCA2 germline mutations. BRCA1/2 mutations play an important role not only in determining the clinical prognosis of breast cancer but also in the survival curves. Since this risk factor is known, a significant amount of the healthcare burden can be reduced by taking preventive measures among people with a known history of familial breast cancer. There is increasing evidence that phytochemicals of nutrients and supplements help in the prevention and cure of BRCA-related cancers by different mechanisms such as limiting DNA damage, altering estrogen metabolism, or upregulating expression of the normal BRCA allele, and ultimately enhancing DNA repair. This manuscript reviews different approaches used to identify potential phytochemicals to mitigate the risk of familial breast cancer with BRCA mutations. The findings of this review can be extended for the prevention and cure of any BRCAmutated cancer after proper experimental and clinical validation of the data.

Joubert Syndrome with a Rare Ocular Phenotype: Coloboma with Retrobulbar Cysts - A Case Report.

Joubert syndrome (JS) is a rare, autosomal recessive, genetic syndrome that derives from the defects in a sensory organelle, the primary cilia. It is a multiorgan disorder affecting the brain, kidneys, liver, and eyes. The most common presenting feature in the newborn period is hypotonia, abnormal eye movements, irregular breathing pattern, characterized by episodic hyperpnea and apnea, later on, ataxia, and developmental retardation. Besides, a range of highly variable, systemic and ocular features can be present. We report a case of 2-month-old female infant, the product of a consanguineous marriage, with a sibling affected by JS, presenting with intermittent hyperpnea, apnea, facial dysmorphism, strabismus, oculomotor apraxia, proptosis, retinal dystrophy, chorioretinal coloboma, and large retrobulbar cysts communicating with the coloboma. Magnetic resonance imaging of the brain revealed the characteristic neuroradiologic finding, the "molar tooth sign." The child does not fix or follow the light, and the visual prognosis with all the ocular features of the syndrome present is extremely poor. In addition to adding to the diversity of ocular phenotypes, this case reiterates the importance of identifying the syndrome, understanding the varied ocular phenotypic presentations, need for further research on causative genes, prenatal diagnosis in affected families, interventions, and adequate genetic counseling.

DNA marker based diversity across rice genotypes and advanced breeding lines bred for temperate regions of North-West India.

BACKGROUND: Characterization and evaluation of plant genetic resources play an important role for their utilization in the crop improvement programmes. METHODS AND RESULTS: This study involves the agro-morphological and cooking quality besides, molecular characterization of 51 genotypes/advance breeding lines of rice from Kashmir Himalayas. Significant variability was observed for all agro-morphological and cooking quality traits among all the studied genotypes. Cluster analysis using UPGMA method divided the genotypes into two major clusters having 15 and 36 genotypes. Thirty eight genotypes screened using 24 SSR markers detected 48 alleles with 2.0 alleles for each locus with average polymorphism information content (PIC) of 0.37. High polymorphism information content (PIC) values was observed for the primers RM263 (0.67), RM159 (0.59) and RM333 (0.50). Furthermore, out of 38 SSR markers screened on 192 temperate rice germpalsm lines, R4M17 accurately differentiated indica and temperate japonica genotypes amplifying 220 bp and 169 bp, respectively. Accordingly, 15 genotypes were reported as indica and 28 temperate japonica in addition to 149 genotypes as intermediate types. CONCLUSION: The information on marker-based diversity and performance based on cooking quality and agronomic traits helped to select the most divergent lines for crossing. Also the analysis was useful to classify the temperate germplasm into indica and temperate japonica. The classification could be helpful to devise a strategy for inter-sub species hybridization to breed for improved rice varieties.

On societal response to pandemics: linking past experiences to present events.

There is a need for a factual understanding of the historical impact of pandemics in the world. Against this backdrop, this study provides a historical understanding of societal behaviour and responses to pandemics. Inferences are primarily drawn from a literature review from the past and present. The present analysis also reflects the ongoing COVID-19 pandemic in the world and India while providing a novel perspective to understand public health practices in a global context. It suggests the need for a more synchronised health response in pandemics while highlighting the uncertainties and challenges with historical evidence and comparisons to the ongoing pandemic. An emphasis is on learning from historical evidence and ascertaining how these retrospective diagnoses help make arguments about health and illness in our present moment.

Combination of Strobilurin and Triazole Chemicals for the Management of Blast Disease in Mushk Budji -Aromatic Rice.

Rice blast is considered one of the most important fungal diseases of rice. Although diseases can be managed by using resistant cultivars, the blast pathogen has successfully overcome the single gene resistance in a short period and rendered several varieties susceptible to blast which were otherwise intended to be resistant. As such, chemical control is still the most efficient method of disease control for reducing the losses caused due to diseases. Field experiments were conducted over two successive years, 2018 and 2019, in temperate rice growing areas in northern India. All the fungicides effectively reduced leaf blast incidence and intensity, and neck blast incidence under field conditions. Tricyclazole proved most effective against rice blast and recorded a leaf blast incidence of only 8.41%. Among the combinations of fungicides, azoxystrobin + difenoconazole and azoxystrobin + tebuconazole were highly effective, recording a leaf blast incidence of 9.19 and 10.40%, respectively. The chemical combination mancozeb + carbendazim proved less effective in controlling the blast and it recorded a disease incidence of 27.61%. A similar trend was followed in neck blast incidence with tricyclazole, azoxystrobin + difenoconazole, and azoxystrobin + tebuconazole showing the highest levels of blast reductions. It is evident from the current study that the tested fungicide combinations can be used as alternatives to tricyclazole which is facing the challenges of fungicide resistance development and other environmental concerns and has been banned from use in India and other countries. The manuscript may provide a guideline of fungicide application to farmers cultivating susceptible varieties of rice.

Clinical Outcomes Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Treated With Liposomal Irinotecan.

BACKGROUND: The NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this. METHODS: This real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology. RESULTS: There were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score <2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively. CONCLUSIONS: Patients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.

Phase I trial of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy for the treatment of metastatic pancreatic cancer.

The safety of oncolytic adenovirus-mediated suicide and interleukin-12 (IL 12) gene therapy was evaluated in metastatic pancreatic cancer patients. In this phase I study, a replication-competent adenovirus (Ad5-yCD/mutTKSR39 rep-hIL-12) expressing yCD/mutTKSR39 (yeast cytidine deaminase/mutant S39R HSV-1 thymidine kinase) and human IL-12 (IL 12) was injected into tumors of 12 subjects with metastatic pancreatic cancer (T2N0M1-T4N1M1) at escalating doses (1 × 1011, 3 × 1011, or 1 × 1012 viral particles). Subjects received 5-fluorocytosine (5-FC) therapy for 7 days followed by chemotherapy (FOLFIRINOX or gemcitabine/albumin-bound paclitaxel) starting 21 days after adenovirus injection. The study endpoint was toxicity through day 21. Experimental endpoints included measurements of serum IL 12, interferon gamma (IFNG), and CXCL10 to assess immune system activation. Peripheral blood mononuclear cells and proliferation markers were analyzed by flow cytometry. Twelve patients received Ad5-yCD/mutTKSR39 rep-hIL-12 and oral 5-FC. Approximately 94% of the 121 adverse events observed were grade 1/2 requiring no medical intervention. Ad5-yCD/mutTKSR39 rep-hIL-12 DNA was detected in the blood of two patients. Elevated serum IL 12, IFNG, and CXCL10 levels were detected in 42%, 75%, and 92% of subjects, respectively. Analysis of immune cell populations indicated activation after Ad5-yCD/mutTKSR39 rep-hIL-12 administration. The median survival of patients in the third cohort is 18.1 (range, 3.5-20.0) months. The study maximum tolerated dose (MTD) was not reached.

COVID-19 and Cancer: Lessons Learnt from a Michigan Hotspot.

(1) Background: Outcomes with coronavirus disease 2019 (COVID-19) have been worse in those with comorbidities and amongst minorities. In our study, we describe outcomes amongst cancer patients in Detroit, a major COVID-19 hotspot with a predominant inner-city population. (2) Methods: We retrospectively analyzed 85 patients with active invasive cancers who were infected with COVID-19. The primary outcome was death or transition to hospice. (3) Results: The majority were males (55.3%, n = 47), ≤70 years old (58.5%, n = 50), and African Americans (65.5%, n = 55). The most common primary site was prostate (18.8%, n = 16). Inpatient admission was documented in 85.5% (n = 73), ICU admission in 35.3% (n = 30), and primary outcome in 43.8% (n = 32) of hospitalized patients. On a multivariate analysis, factors associated with increased odds of a primary outcome included an age of >70 years versus ≤70 years (OR 4.7, p = 0.012) and of male gender (OR 4.8, p = 0.008). Recent cancer-directed therapy was administered in 66.7% (n = 20) of ICU admissions versus 39.5% (n = 17) of general floor admissions (Chi-square p-value of 0.023). (4) Conclusions: High rates of mortality/transition to hospice and ICU utilization were noted amongst our patients with active invasive cancer, following a COVID-19 infection. Men and those of >70 years of age had a greater than four-fold increase in odds of death or transition to hospice.

Exceptional Response to A Single Cycle of Immunotherapy in a Lynch Syndrome Patient with Metastatic Pancreatic Adenocarcinoma.

BACKGROUND Pancreatic adenocarcinoma (PDA) is associated with an 8.6-fold increased risk in Lynch syndrome patients. Here, we report the case of a Lynch syndrome PDA patient with an exceptional response to a single cycle of pembrolizumab immunotherapy. CASE REPORT A 65-year-old male patient with Lynch syndrome mismatch repair (MMR) deficient PDA with metastatic liver disease, received 1 cycle of pembrolizumab (200 mg) after progressing on 2 standard lines of treatment. His initial computed tomography (CT) showed 3×2.5 cm PDA. At that time, the disease was considered borderline resectable, and the patient received 6 cycles of FOLFIRINOX followed by chemoradiotherapy with capecitabine. A follow-up CT scan showed multiple new liver lesions. The biopsy showed metastatic PDA and tumor tissue demonstrated high microsatellite instability with abnormal/lost expression of MLH1 and PMS2 proteins. The patient was started on pembrolizumab. Only 1 cycle was given due to the development of thromboembolic complications: pulmonary embolism and myocardial infarction. His thrombophilia workup was negative. Restaging CT scans at 3, 6, and 9 months after 1 cycle of pembrolizumab revealed an excellent response with shrinkage of liver lesions. Restaging at 11 months showed the eventual resolution of most liver lesions. No new metastatic disease developed. A repeat biopsy of the dominant liver lesion showed no morphological evidence of PDA. CONCLUSIONS Only 1 cycle of pembrolizumab resulted in clinical complete response and pathologic response in metastatic PDA. We emphasize the importance of testing for MMR status and treating with immunotherapy in metastatic PDA patients with MMR deficiency.

Neoadjuvant Phase II Trial of Chemoradiotherapy in Patients With Resectable and Borderline Resectable Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.

Colorectal Cancer and Nutrition.

Colorectal Cancer is the third most common cancer diagnosed in the US. While the incidence and the mortality rate of colorectal cancer has decreased due to effective cancer screening measures, there has been an increase in number of young patients diagnosed in colon cancer due to unclear reasons at this point of time. While environmental and genetic factors play a major role in the pathogenesis of colon cancer, extensive research has suggested that nutrition may play both a causal and protective role in the development of colon cancer. In this review article, we aim to provide a review of factors that play a major role in development of colorectal cancer.

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours.

BACKGROUND: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. METHODS: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). CONCLUSIONS: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

Marker-assisted introgression of three dominant blast resistance genes into an aromatic rice cultivar Mushk Budji.

Modern high yielding rice varieties have replaced most of the traditional cultivars in recent past. Mushk Budji, is one such short grained landrace known for its aroma and exquisite quality, however, is highly susceptible to blast disease that has led to considerable decline in its area. Mushk Budji was crossed to a triple-gene donor line, DHMAS 70Q 164-1b and followed through marker-assisted foreground and background selection in first and second backcross generations that helped to incorporate blast resistance genes Pi54, Pi1 and Pita. Marker-assisted background selection was carried out using 78 SSR and STS markers that helped to reduce linkage drag around the genes Pi54, Pi1 and Pita to 2.74, 4.60 and 2.03 Mb, respectively. The three-gene lines in BC2F2:3 were genotyped using 50 K SNP chip and revealed more than 92% genome similarity to the RP. 2-D gel assay detected differentially expressing 171 protein spots among a set of backcross derived lines, of which 38 spots showing match score of 4 helped us to calculate the proteome recovery. MALDI-TOF analysis helped to detect four significant proteins that were linked to quality and disease resistance. The improved lines expressed resistance to blast under artificial and natural field conditions.