Enhancing cancer immunotherapy: Exploring strategies to target the PD-1/PD-L1 axis and analyzing the associated patent, regulatory, and clinical trial landscape.

Cancer treatment modalities and their progression is guided by the specifics of cancer, including its type and site of localization. Surgery, radiation, and chemotherapy are the most often used conventional treatments. Conversely, emerging treatment techniques include immunotherapy, hormone therapy, anti-angiogenic therapy, dendritic cell-based immunotherapy, and stem cell therapy. Immune checkpoint inhibitors' anticancer properties have drawn considerable attention in recent studies in the cancer research domain. Programmed Cell Death Protein-1 (PD-1) and its ligand (PD-L1) checkpoint pathway are key regulators of the interactions between activated T-cells and cancer cells, protecting the latter from immune destruction. When the ligand PD-L1 attaches to the receptor PD-1, T-cells are prevented from destroying cells that contain PD-L1, including cancer cells. The PD-1/PD-L1 checkpoint inhibitors block them, boosting the immune response and strengthening the body's defenses against tumors. Recent years have seen incredible progress and tremendous advancement in developing anticancer therapies using PD-1/PD-L1 targeting antibodies. While immune-related adverse effects and low response rates significantly limit these therapies, there is a need for research on methods that raise their efficacy and lower their toxicity. This review discusses various recent innovative nanomedicine strategies such as PLGA nanoparticles, carbon nanotubes and drug loaded liposomes to treat cancer targeting PD-1/PD-L1 axis. The biological implications of PD-1/PD-L1 in cancer treatment and the fundamentals of nanotechnology, focusing on the novel strategies used in nanomedicine, are widely discussed along with the corresponding guidelines, clinical trial status, and the patent landscape of such formulations.

Understanding immune checkpoints and PD-1/PD-L1-mediated immune resistance towards tumour immunotherapy.

Immunotherapy has emerged as a transformative approach in the treatment of various cancers, offering new hope for patients previously faced with limited treatment options. A cornerstone of cancer immunotherapy lies in targeting immune checkpoints, particularly the programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) pathway. Immune checkpoints serve as crucial regulators of the immune response, preventing excessive immune activity and maintaining self-tolerance. PD-1, expressed on the surface of T cells, and its ligand PD-L1, expressed on various cell types, including cancer cells and immune cells, play a central role in this regulatory process. Although the success rate associated with these immunotherapies is very promising, most patients still show intrinsic or acquired resistance. Since the mechanisms related to PD-1/PD-L1 resistance are not well understood, an in-depth analysis is necessary to improve the success rate of anti-PD-1/PD-L1 therapy. Hence, here we provide an overview of PD-1, its ligand PD-L1, and the resistance mechanism towards PD-1/PD-L1. Furthermore, we have discussed the plausible solution to increase efficacy and clinical response. For the following research, joint endeavours of clinicians and basic scientists are essential to address the limitation of resistance towards immunotherapy.

Cor triloculare biventriculare with left superior vena cava.

Cor triloculare biventriculare is a rare congenital malformation of the heart in which there is a complete absence of the atrial septum. It is usually associated with other anomalies like complete atrioventricular canal defect, polysplenic syndrome, isolated dextrocardia, Ellis-van Creveld syndrome, or persistent left superior vena cava. We report a case of a stillborn male foetus of 35 weeks gestation with common atrium, complete atrioventricular canal defect, and persistent left superior vena cava. The possible embryological basis and clinical implication of this variation are discussed.

Leiomyosarcoma of uterus--a case report.

Leiomyosarcoma of uterus is a very rare malignant mesenchymal tumour of uterus. It may arise from the uterine myometrium de novo or may be transformed from a pre-existing benign leiomyoma. A 55-year-old female presenting with 20-22 weeks size of uterus and bleeding per vagina was clinically diagnosed as a case of leiomyoma uteri and cervical polyp, was subjected to abdominal hysterectomy. The tumour mass was later confirmed histologically as leiomyosarcoma of uterus presumed to be transformed from pre-existing leiomyoma uteri.

Genetic polymorphisms of red cell enzymes in tribes of Andhra Pradesh, India.

The genetic heterogeneity of some common red cell enzyme markers among four endogamous tribal populations namely Konda Dora, Kotia, Bod Mali and Manzai Mali was investigated by starch/polyacrylamide/cellulose acetate gel electrophoresis. ACP, ESD, PGM1, G6PD, AK1, ADA, 6PGD enzymes and haemoglobin exhibited a polymorphism. PGM2, LDH, MDH, SOD, GOT, CA1, CA2 and GPI were monomorphic. A slow variant of SOD similar to that found in SOD 2-1 heterozygote was observed with a frequency of 1.31% among Kotia tribe. Most populations of the present study were in Hardy-Weinberg equilibrium for the majority of the genetic markers examined. The results are discussed in the light of available data on other Andhra populations.

Paraganglioma in the nasopharynx.

A 50-year old male presented with swollen right eyelids, bleeding per nostrils and a vague left post-auricular swelling for 4 months. Posterior rhinoscopy revealed one pinkish polypoidal mass in the posterior nare and roof of nasopharynx. FNAC from the post-auricular swelling suggested metastatic undifferentiated carcinoma. Incisional biopsy was done form the nasopharynx and histopathological examination proved it to be a malignant paraganglioma. The case is reported for its rarity.

CT guided fnac of nasopharynx: A new diagnostic tool for early and rapid detection of Nasopharyngeal Carcinoma.

Early detection of nasopharyngeat carcinoma (NPC) still remains a. ekalleng to the clinicians because of its nonspecific early signs and symptom, difficulty in the eramaation of the nasopharynx and also becuase of the disease's early loco- regional spread. For an.early and rapid detection of this diseas a new diagnostic fool- CT guided FNAC of nasopharyns is interdadeced here in the diagnostic armamentarium of the head and neck cancers. In this prospective study 30 clinically suspectedcases of NPC are subjected to this new diagnostic tool along with tht other dignastic measures like radiological and pathological studies. The technique is found to be quite reliable in the diagnosis of NPC with a sensitivity of 63.2% and. a specificity of 100% The overall actaracy of the technique is 76.7% This, novel technique is fast and reliable, well tolerated by the patients with few complications, and if performed properly, can contain costs while maintaining high dianastic efficency.

Genetic serum protein markers in eight south Indian caste and tribal populations.

A total of n = 769 unrelated male and female individuals from eight endogamous caste (Brahmin, Kapu, Yadava, Relli) and tribal (Bagatha, Kotia, Manne Dora, Konda Dora) populations living in various districts of Andhra Pradesh (India) have been typed for haptoglobin (HP) types and transferrin (TF), group specific component (GC) and alpha 1-antitrypsin (PI) subtypes. The genetic heterogeneity among these population groups is considerable. This can be explained by lacking or at least only minimal gene flow among these caste and tribal groups, by which differences in their genetic profiles caused by locally acting genetic differentiation factors such as drift could be preserved.