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Oncotarget Jul 2024
Topics: Humans; Male; Prostatic Neoplasms, Castration-Resistant; Circulating Tumor DNA; Neoplasm Metastasis; Treatment Outcome; Biomarkers, Tumor
PubMed: 38953903
DOI: 10.18632/oncotarget.28599 -
Oncotarget Jul 2024Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib...
Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.
Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). We previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. We hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer. We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and . TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition. Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status . TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms. The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.
Topics: Humans; Trifluridine; Phenylurea Compounds; Animals; Pyridines; Drug Synergism; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Neovascularization, Pathologic; Xenograft Model Antitumor Assays; Neoplastic Stem Cells; Gastrointestinal Neoplasms; Uracil; Mice; STAT3 Transcription Factor; Thymine; Drug Combinations; Cell Line, Tumor; Pyrrolidines; Mutation; Antineoplastic Combined Chemotherapy Protocols; MAP Kinase Signaling System; Signal Transduction; Cell Proliferation; Angiogenesis
PubMed: 38953895
DOI: 10.18632/oncotarget.28602 -
ELife Jul 2024While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility....
While the involvement of actin polymerization in cell migration is well-established, much less is known about the role of transmembrane water flow in cell motility. Here, we investigate the role of water influx in a prototypical migrating cell, the neutrophil, which undergoes rapid, directed movement to sites of injury, and infection. Chemoattractant exposure both increases cell volume and potentiates migration, but the causal link between these processes are not known. We combine single-cell volume measurements and a genome-wide CRISPR screen to identify the regulators of chemoattractant-induced neutrophil swelling, including NHE1, AE2, PI3K-gamma, and CA2. Through NHE1 inhibition in primary human neutrophils, we show that cell swelling is both necessary and sufficient for the potentiation of migration following chemoattractant stimulation. Our data demonstrate that chemoattractant-driven cell swelling complements cytoskeletal rearrangements to enhance migration speed.
Topics: Humans; Neutrophils; Cell Movement; Cell Size; Sodium-Hydrogen Exchanger 1; Chemotactic Factors
PubMed: 38953885
DOI: 10.7554/eLife.90551 -
ELife Jul 2024An influx of water molecules can help immune cells called neutrophils to move to where they are needed in the body.
An influx of water molecules can help immune cells called neutrophils to move to where they are needed in the body.
Topics: Neutrophils; Humans; Animals; Water
PubMed: 38953882
DOI: 10.7554/eLife.100032 -
Indian Journal of Public Health Apr 2024
Topics: Humans; Saliva; Nipah Virus; Henipavirus Infections; India
PubMed: 38953831
DOI: 10.4103/ijph.ijph_1185_23 -
Indian Journal of Public Health Apr 2024An outbreak of dengue fever struck Tikarapada village, Rayagada district (April 2020). Among 117 fever cases, 49 tested positive for the dengue NS1 antigen. To identify...
An outbreak of dengue fever struck Tikarapada village, Rayagada district (April 2020). Among 117 fever cases, 49 tested positive for the dengue NS1 antigen. To identify mosquito-related factors in the outbreak, a survey of 101 houses found Aedes breeding sites in 11.6% of containers. Aedes aegypti (79%) and Aedes albopictus (21%) emerged from collected pupae. The village exhibited high (house index = 24.8), (container index = 11.6), (pupal index = 32.7), and (Breteau index = 40.6) indices. The findings confirmed the presence of Aedes and ample breeding sites, suggesting their role in the outbreak. A report recommending integrated vector control measures was submitted to district and state health authorities.
Topics: Dengue; Aedes; Animals; Disease Outbreaks; Humans; India; Mosquito Vectors; Male; Adult; Female; Adolescent; Child; Middle Aged; Dengue Virus; Young Adult; Mosquito Control; Child, Preschool
PubMed: 38953830
DOI: 10.4103/ijph.ijph_749_23 -
Indian Journal of Public Health Apr 2024Cancer patients suffer from complicated chemotoxicity. Pharmacogenomics can help stratify patients by predicting their response to treatment and susceptibility toward...
Cancer patients suffer from complicated chemotoxicity. Pharmacogenomics can help stratify patients by predicting their response to treatment and susceptibility toward severe side effects. The spindle-assembly checkpoint (SAC) is an important pathway that is activated by platinum and taxane compounds and plays a crucial role in their cytotoxic activity. This study investigated a SAC component, Budding Uninhibited by Benzimidazoles 3 (BUB3), its expression, and genetic variants in advanced ovarian cancer patients treated with paclitaxel-carboplatin chemotherapy. Among 80 patients, BUB3 expression correlated with chemosensitivity, suggesting its potential as a predictive marker for chemotherapy response. However, high BUB3 expression was associated with a higher risk of poor survival. In addition, genetic polymorphisms in BUB3 (rs11248416 and rs11248419) were significantly linked to chemotherapy-related toxicities, with rs11248416 showing a negative impact on the patient's physical quality of life.
Topics: Humans; Female; Paclitaxel; Ovarian Neoplasms; Carboplatin; Middle Aged; M Phase Cell Cycle Checkpoints; Antineoplastic Combined Chemotherapy Protocols; Polymorphism, Single Nucleotide; Cell Cycle Proteins; Adult; Antineoplastic Agents; Quality of Life
PubMed: 38953826
DOI: 10.4103/ijph.ijph_809_23 -
Indian Journal of Public Health Apr 2024Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases... (Review)
Review
Oropharyngeal cancers (OPCs) in Asia account for 42% of the global burden and over 50% of related deaths. Human papillomavirus (HPV) is involved in over 70% of OPC cases in the Western hemisphere, but its role in the Eastern hemisphere is unclear. This study reviews OPC epidemiology, including prevalence, etiological factors (such as smokeless tobacco and HPV), and their interaction. Among the SEAR countries, India had the highest incidence of HPV-related OPCs at 38.4%, while data were unavailable for most African countries, with only a 14% incidence reported. Conversely, the American region exhibited one of the highest HPV positivity rates, reaching up to 65% in different states of the USA, while Brazil reported an incidence of up to 38%. In the European Union, the UK had the highest incidence of HPV-associated OPC, reaching up to 52%. In the Western Pacific region, New Zealand demonstrated the highest incidence at up to 78%. Smokeless tobacco consumption was higher in SEAR countries, which had a relatively lower incidence of HPV infection, suggesting a negative correlation between the two. Based on our literature search, the most common detection methods used globally are immunohistochemistry for p16 and polymerized chain reaction. OPCs are a global health concern, and proper identification and classification are vital. HPV-driven cancers have better survival rates, emphasizing the need for focused research on specific problem areas based on the burden of HPV-positive or HPV-negative cancers.
Topics: Humans; Oropharyngeal Neoplasms; Papillomavirus Infections; Global Health; Incidence; Prognosis; Prevalence; Tobacco, Smokeless; Papillomaviridae; Human Papillomavirus Viruses
PubMed: 38953816
DOI: 10.4103/ijph.ijph_827_23 -
Indian Journal of Public Health Apr 2024Several sporadic cases and outbreaks of Zika virus disease have been reported from different states of India.
BACKGROUND
Several sporadic cases and outbreaks of Zika virus disease have been reported from different states of India.
OBJECTIVES
This paper explored the possibility of any ongoing transmission of Zika virus (ZIKV) in the Bhopal region of Central India, where the last outbreak of this disease was reported in 2018.
MATERIALS AND METHODS
We screened a group of 75 febrile patients who had already tested negative for the locally endemic causes of fever like dengue, chikungunya, enteric fever, malaria, and scrub typhus and two groups of asymptomatic healthy individuals represented by blood donors (n = 75) and antenatal mothers (n = 75). We tested blood samples of febrile patients for ZIKV RNA using real-time polymerase chain reaction (PCR), and for the healthy individuals, we determined anti-zika immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay.
RESULTS
ZIKV RNA was not detected in any of the 75 samples tested by real-time PCR assay. Among the voluntary blood donors and antenatal mothers, a total of 10 (15.38%) and 5 (6.66%) individuals were found to be seropositive for anti-ZIKV IgG antibodies, respectively. The seropositive group was found to have higher age 33.06 (±10.83) years as compared to seronegative individuals 26.60 (±5.12) years (P = 0.037).
CONCLUSION
This study, which is the first survey of seroprevalence of anti-Zika antibodies from India, reports an overall seropositivity rate of 10% for anti-Zika antibodies among the healthy population, suggesting an ongoing, low level, silent transmission of ZIKV in the local community.
Topics: Humans; India; Zika Virus Infection; Seroepidemiologic Studies; Adult; Female; Pilot Projects; Male; Zika Virus; Immunoglobulin G; Young Adult; Antibodies, Viral; Middle Aged; RNA, Viral; Adolescent; Enzyme-Linked Immunosorbent Assay; Real-Time Polymerase Chain Reaction
PubMed: 38953800
DOI: 10.4103/ijph.ijph_1098_23 -
Parasite (Paris, France) 2024Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies...
Schistosomiasis is of medical and veterinary importance. Despite the critical situation of schistosomiasis in sub-Saharan Africa, few molecular epidemiological studies have been carried out to determine the role of animals in its transmission. In Mali, it has been over three decades since the last molecular study of animal schistosomes was carried out. It is now urgent to identify circulating strains of the parasite because of potential interactions with other schistosome species, which could complicate disease control. The aim of our work was to study the composition and genetic structure of schistosome populations collected from cattle. The prevalence of schistosome was 23.9%, with the prevalences of Schistosoma bovis (Sb) and S. curassoni (Sc) estimated at 12.6% and 9.8%, respectively. No hybrid strains or S. haematobium were found. The parasites displayed distinct geographical distribution with Sb dominant in Bamako (78.8% and 98% in Central Bamako Slaughterhouse and Sabalibougou Slaughterhouses, respectively) and Sc dominant in Kayes (95.3%). Of the 476 parasites with a complete genetic profile, 60.4% were pure Sc, and were mainly from Kayes. We identified two clusters at the site level (Fst of 0.057 and 0.042 for Sb and Sc, respectively). Cluster 1 was predominantly composed of pure Sb parasites and cluster 2 was mainly composed of pure Sc parasites, from Bamako and Kayes, respectively. Our study shows that cattle schistosomiasis remains endemic in Mali with S. bovis and S. curassoni. A robust genetic structure between the different schistosome populations was identified, which included two clusters based on the geographical distribution of the parasites.
Topics: Animals; Cattle; Mali; Schistosoma; Cattle Diseases; Schistosomiasis; Prevalence; Genetic Variation; Genetics, Population; DNA, Helminth
PubMed: 38953782
DOI: 10.1051/parasite/2024035