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Since the ancient days human beings have fought evil forces with all the available might; be it spiritual and/or muscle power. Let us name the two confronting groups as defenders and infiltrators. Now considering the Indian perspective, we assume its position to be defenders as could be seconded by availing historical facts. However, in this endeavour knowingly or unknowingly the knowledge that the Veda's say "YathaPindetathaBrahmande" which means what is going on within you is same as what is going on in the universe Or what arrangements exists at the micro level exists at the macro level also seems to have been sidelined as perceivedby the fall in values and ethical practices albeit worldwide leading to tremendous loss of life and property for the defenders during confrontations. This may be attributed to the absence of a bench mark for comparing the restraint efficiency of the existing defence mechanisms and hence inability to correct the system's output deviations if any in this age old institution of defence and arms. This paper therefore attempts to identify the similarities in them (macro) with the body cell (micro) defence mechanisms when subjected to sources of decay in the practice of ethos and values so that ways and means could be found for understanding and achieving a successful restraint strategy leading to maximum destruction of infiltrators and minimum loss for the defenders. [ABSTRACT FROM AUTHOR]

CD8 + T cell responses are the foundation of the recent clinical success of immunotherapy in oncologic indications. Although checkpoint inhibitors have enhanced the activity of existing CD8 + T cell responses, therapeutic approaches to generate Ag-specific CD8 + T cell responses have had limited success. Here, we demonstrate that cytosolic delivery of Ag through microfluidic squeezing enables MHC class I presentation to CD8 + T cells by diverse cell types. In murine dendritic cells (DCs), squeezed DCs were ∼1000-fold more potent at eliciting CD8 + T cell responses than DCs cross-presenting the same amount of protein Ag. The approach also enabled engineering of less conventional APCs, such as T cells, for effective priming of CD8 + T cells in vitro and in vivo. Mixtures of immune cells, such as murine splenocytes, also elicited CD8 + T cell responses in vivo when squeezed with Ag. We demonstrate that squeezing enables effective MHC class I presentation by human DCs, T cells, B cells, and PBMCs and that, in clinical scale formats, the system can squeeze up to 2 billion cells per minute. Using the human papillomavirus 16 (HPV16) murine model, TC-1, we demonstrate that squeezed B cells, T cells, and unfractionated splenocytes elicit antitumor immunity and correlate with an influx of HPV-specific CD8 + T cells such that >80% of CD8s in the tumor were HPV specific. Together, these findings demonstrate the potential of cytosolic Ag delivery to drive robust CD8 + T cell responses and illustrate the potential for an autologous cell-based vaccine with minimal turnaround time for patients., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Despite cervical cancer being considered a preventable disease, it still remains the second most common malignancy in women worldwide, with a higher incidence in underdeveloped countries. Human papillomavirus (HPV) is considered the causative agent of cervical cancer. The major mechanisms through which HPV contributes to neoplastic initiation and progression include the activity of 2 viral oncoproteins, E6 and E7, which interfere with critical cell cycle tumor suppressive proteins, p53 and retinoblastoma (Rb) protein. However, HPV infection alone is not sufficient to induce malignant transformation, and other significant cofactors contribute to the multi-step process of tumor formation, such as individual genetic variations as well as environmental factors. However, these cofactors are not important in the absence of HPV. Papanicolaou testing (Pap smear) and HPV DNA testing are tools used in the screening and diagnosis of cervical neoplastic lesions. Vaccination against HPV appears to be cost-effective in the prevention of HPV infection. A thorough understanding of the mechanisms that underline HPV carcinogenesis may result in the development of sophisticated targeted therapeutic approaches, such as antisense oligonucleotides against HPV oncoproteins.

Appendiceal carcinoma is a very rare clinical entity, constituting 1% of all colorectal malignancies and 1% of all appendectomy specimens. Appendiceal malignancies often present atypically, thus creating diagnostic challenges. We present a patient with mucinous carcinoma of the appendix who presented with hematuria and abdominal pain. Similar case reports are extremely rare in the literature, while typical presentations of appendiceal carcinoma include abdominal pain, abdominal mass, early satiety, nausea, and iron-deficiency anemia. Initially, the diagnostic investigation in our patient was focused on urinary tract disorders, but ultimately resulted in finding a mucinous appendiceal carcinoma. The carcinoma had invaded the urinary bladder and was disseminated in the peritoneal cavity. Aggressive cytoreductive surgery is the most common therapeutic approach for disseminated tumors, often followed by intraperitoneal chemotherapy. However, treatment should be individualized based on patient-specific parameters, such as the presence of comorbidities, performance status, as well as the presence of metastatic disease. Our patient had optimal cytoreduction with subsequent systemic therapy with 5-fluorouracil, leucovorin, oxaliplatin, and bevacizumab, a monoclonal antibody directed against vascular endothelial growth factor. She completed her treatment regimen without complications and is currently being restaged. An integrative approach is required in the diagnostic investigation and management of appendiceal malignancies.